tbuckley/cabot-search huggingface dataset:
SAT0154 Bisphosphonates and upper gi problems – what is the evidence?
Authors: DC Bauer, B Cryor
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Upper gastrointestinal (UGI) tract mucosal irritation has been reported for a variety of bisphosphonates, including pamidronate, etidronate, clodronate, alendronate (ALN), tiludronate, and risedronate (RIS). <h3>Objectives</h3> To use evidence-based medicine to rate and summarise the evidence regarding bisphosphonates and UGI problems. <h3>Methods</h3> Review and interpretation of published studies. <h3>Results</h3> Although the clinical relevance of short-term, transient endoscopic findings is uncertain, one endoscopic study reported a higher incidence of gastric lesions for ALN vs RIS, and others reported no difference for ALN vs RIS or placebo.<sup>1–4</sup> These endoscopic studies differed in regard to blinding, duration, and control. Endoscopy trials that were appropriately blinded and of longer duration (4–10 wks) found no difference between ALN and RIS or placebo, even at the higher doses used for once-weekly dosing<sup>4</sup> or to treat Paget's disease.<sup>3</sup>Randomised, blinded, controlled trials (RCTs) with clinically relevant GI endpoints represent the highest level of evidence, and tens of thousands of patients have participated in RCTs of ALN and RIS for up to 7 years. UGI complaints were common in these studies (~30% in the first year), and were comparable to placebo. In particular, the incidence of more worrisome UGI events (including esophageal events, and gastroduodenal perforations, ulcers, and bleeds) was low and comparable to the placebo group, even in high risk subgroups, among 6459 women randomised to ALN or placebo for up to 4.5 years in the Fracture Intervention Trial.<sup>5</sup> Furthermore, two independent RCTs of patients who had previously reported intolerance to bisphosphonate reported that the large majority (~85%) were able to continue ALN or RIS when treatment was resumed, and the permanent discontinuation rates were no different from the placebo group.<sup>6,7</sup> <h3>Conclusion</h3> Based on extensive data from large RCTs, we conclude that any increase above placebo in clinically relevant UGI problems related to bisphosphonate use is very low – too low to detect in trials involving thousands of participants during several years of follow-up. <h3>References</h3> Lowe C, <i>et al</i>. Am J Gastroenterol. 2000;95:634–40 Lanza F, <i>et al</i>. Gastroenterology 2000;119:631–8 Lanza F, <i>et al</i>. Am J Gastroenterol. 2000;95:3112–17 Lanza F, <i>et al</i>. Arthritis Rheum. 2000;43(Suppl 9):S198 Bauer DC, <i>et al</i>. Arch Intern Med. 2000;160:517–25 Miller PD, <i>et al</i>. Clin Ther. 2000;22(12):1433–42 Adachi JD, <i>et al</i>. Arthritis Rheum 2000;43(Suppl 9):S202
Microbiome markers are early predictors of acute GVHD in allogeneic hematopoietic stem cell transplant recipients
Authors: Raffaella Greco, Rosamaria Nitti, Nicasio Mancini, Renée Pasciuta, Francesca Lorentino, Maria Teresa Lupo-Stanghellini, Maria Chiara Barbanti, Nicola Clementi, Fabio Giglio, Daniela Clerici, Sarah Marktel, Andrea Assanelli, Matteo G. Carrabba, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Massimo Clementi, Fabio Ciceri
Journal: Blood (2020)
US Supreme Court leans toward upholding Obamacare
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

The US Supreme Court heard oral arguments yesterday (10 November) in the case attempting to overturn the Affordable Care Act, widely known as Obamacare. The court will issue its decision before the end of its term in June 2021.

Questions by two conservative justices, chief justice John Roberts Jr and associate justice Brett Kavanaugh, indicated that they were leaning toward preserving the act, as did comments by the liberal justices Stephen Breyer, Sonia Sotomayor, and Elena Kagan. This would suggest a 5-4 ruling in favor of preserving Obamacare. The other four justices are conservative.

Obamacare, President Barack Obama’s signature legislation to provide health insurance to more Americans, was passed in November 2010 with only Democrats voting in favor.1 President Donald Trump subsequently promised to repeal Obamacare and replace it with …
Abstract 15568: Profound Increases in Out-of-Hospital Cardiopulmonary Arrest Cases Within Most Metropolitan Municipalities During the COVID-19 Pandemic
Authors: Paul E Pepe, Kevin E McVaney, Lauren M Maloney, Eric Stein Bronsky, James J Augustine, Glenn H Asaeda, Marc K Eckstein, Michael T Osterholm
Journal: Circulation (2020)

Introduction: Even though most EMS systems globally experienced dramatic decreases in call volumes during the COVID-19 pandemic, many also reported unexpected increases in out-of-hospital cardiac arrest (OHCA) cases. Hypothesis: The pervasiveness of COVID-19 in metropolitan cities might be associated with a greater number of OHCA cases as compared to prior years. Methods: Large city EMS system medical directors responsible for about one-quarter of the U.S. population and millions of others in Europe/Australia were asked to tabulate the absolute number of OHCA cases to which EMS responded within their jurisdictions during the first 4 months of 2020. Results were compared to average numbers encountered during 2018 and 2019. A priori, considering the large populations (high corresponding OHCA frequencies) and case complexities, a 15% increase/decrease was to be considered highly significant (usual variation + 4-8% within the 28-31 days/month). Results: Of 35 major U.S. cities reporting to date, most had significant increases in OHCA, particularly in April with 71% (25/35) of the cities seeing a very large (&gt;15%) increase. Nine cities (26%), all experiencing a high prevalence of COVID-19, had &gt;50% (1.5-fold) increases. Three cities with highly-publicized inundations of COVID-19, experienced more than twice as many arrests (3.5-fold in the worst case). Meanwhile, 3 other cities with relatively low COVID-19 impact to date, had significantly fewer cases. Still, combining all of the 35 cities studied, OHCA increased from 5,009 (2 prior years’ average) to 8,701 (74% increase) during April (Fig 1). Participating cities outside the U.S. (e.g., Paris, London, Perth) mirrored these findings. Conclusions: To date, most, but not all, metropolitan cities have clearly experienced significant increases in OHCA that appear to parallel the prevalence of COVID-19 in their respective jurisdictions. These observations and available forensic data are now part of a work in progress.
Abstract 13827: Sleep Quality Improved After Intensified Blood Pressure Lowering Therapy
Authors: Roland E Schmieder, Kristina Striepe, Agnes Bosch, Karin Högerl, Roland Veelken, Julie Kolwelter
Journal: Circulation (2020)

Insufficient and poor sleep on a chronic basis raises blood pressure (BP), the risk of hypertension and cardiovascular disease which in turn further leads to sleep disturbances.In a prospective observational study we tested the hypothesis whether intensification of antihypertensive therapy improves sleep quality Patients with arterial hypertension on multiple drug medication were followed for 3 months if according to the physician‘s perception BP control was insufficient or patients profit from simplification of drug therapy. Intensification of antihypertensive therapy consisted of switching from multiple pills per day to a single pill combination. Office BP readings and out-of-BP measurements were monitored. The abbreviated PITTSBURGH SLEEP INVENTORY (PSQI) was applied to assess sleep duration and quality Results: In 229 patients (mean age 65 years, 62 % were males) office BP decreased from 158 ± 15/92 ± 8 to 132 ± 10/87 ± 8 mmHg (both p&lt;0.001). In parallel, sleep quality improved in 45 % and remained equal/worse in 53 % (p&lt;0.001) after 3 months In patients whose sleep quality improved (N=95) office BP dropped from 160±15/94±10 to 131±8.6/80±7 mmHg (both p&lt;0.001), whereas in patients with equal or worse sleep quality (N=119) BP fell only from 156±15/90±5 to 133±10/80±8 mmHg (both p&lt;0.001). BP fall was significantly greater in those with improved sleep quality as opposed to those with equal/worse sleep quality after 3 months of therapy (4.98±1.5/2.71±0.94 mmHg, p&lt;0.001 and p=0.005, respectively). Change in out-office systolic BP measurements was greater in those with improved as opposed to those with equal/worse sleep quality (5.80±1.9 mmHg, p=0.003). Thus, intensification of antihypertensive treatment by using single pill combination resulted in significant fall in BP accompanied by an improvement in sleep quality. Abstract Sleep quality improved after intensified blood pressure lowering therapy.docx
Abstract 15852: Body Mass Index and Fatal Outcome in Patients Hospitalized for Covid 19
Authors: Gursukhman Sidhu, Saihariharan Nedunchezhian, Laura Padilla-Carrasquillo, nitin sabharwal, Seyed Khalafi, Ali Ayoub, Rohan Samson, THIERRY LEJEMTEL
Journal: Circulation (2020)

Introduction: Obesity may affect COVID-19 outcomes, independent of its association with hypertension, diabetes, chronic obstructive pulmonary disease and other cardiovascular disease. Hypothesis: Is obesity a major determinant of morbidity and mortality in patients with COVID-19? Methods: Retrospective analysis of all confirmed COVID-19 patients hospitalized at University Medical Center in New Orleans, Louisiana between February 1, 2020 to May 1, 2020 was performed. Intensive care unit (ICU) stay and fatal outcomes were analyzed as a function of body mass index (BMI), hypertension, diabetes, hyperlipidemia, and CKD. Risk factors for fatal outcomes were evaluated. Multivariate logistic regression was used to determine odds ratios. P-Value was set at 0.05. Results: From a sample size of 419 patients, 60(14.3%) were admitted to the ICU. Amongst ICU admits, 85% were African American (AA), 61.6% had BMI &gt;30, 48.3% had diabetes, and 30% had chronic kidney disease. Mortality was 91.6% after ICU admission. Out of a total of 419, mortality was the highest in admits with BMI &lt; 25(20.2%) and with BMI &gt;40(20.3%). BMI &gt; 40 was associated with a higher odds of death (Odds ratio: 3.9, 95% Confidence Interval (CI) 1.45-10.5) and ICU admission (OR:3.2 95% CI 1.1-9) after adjustment for age, race, sex and comorbidities. Conclusion: A direct association exists for BMI &gt; 40 and in-hospital death, independent of comorbidities. Caution with aggressive intervention is warranted for such patients on presentation.
Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice
Authors: Muthiah Vaduganathan, Stephen J. Greene, Shuaiqi Zhang, Maria Grau-Sepulveda, Adam D. DeVore, Javed Butler, Paul A. Heidenreich, Joanna C. Huang, Michelle M. Kittleson, Karen E. Joynt Maddox, James J. McDermott, Anjali Tiku Owens, Pamela N. Peterson, Scott D. Solomon, Orly Vardeny, Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (2020)

In May 2020, dapagliflozin was approved by the US Food and Drug Administration (FDA) as the first sodium-glucose cotransporter 2 inhibitor for heart failure with reduced ejection fraction (HFrEF), based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Limited data are available characterizing the generalizability of dapagliflozin to US clinical practice.
Genetics of Anthracycline Cardiomyopathy in Cancer Survivors
Authors: Smita Bhatia
Journal: JACC CardioOncology (2020)

Anthracyclines are an integral part of chemotherapy regimens used to treat a variety of childhood-onset and adult-onset cancers. However, the development of cardiac dysfunction and heart failure often compromises the clinical utility of anthracyclines. The risk of cardiac dysfunction increases with anthracycline dose. This anthracycline-cardiac dysfunction association is modified by several demographic and clinical factors, such as age at anthracycline exposure (<4 years and ≥65 years); female sex; chest radiation; presence of cardiovascular risk factors (diabetes, hypertension); and concurrent use of cyclophosphamide, paclitaxel, and trastuzumab. However, the clinical variables alone yield modest predictive power in detecting cardiac dysfunction. Recently, attention has focused on the molecular basis of anthracycline-related cardiac dysfunction, providing an initial understanding of the mechanism of anthracycline-related cardiomyopathy. This review describes the current state of knowledge with respect to the pathogenesis of anthracycline-related cardiomyopathy and identifies the critical next steps to mitigate this problem.
Abstract 14573: Association of Human Mesenchymal Stem Cell and Lodenafil in Hypoxia-induced Pulmonary Arterial Hypertension
Authors: Grazielle F Silva, Marina Silva, Jaqueline S Da Silva, Allan K Alencar, Tadeu Montagnoli, Bruna Rocha, Guilherme C Montes, Juliana Vasques, Pedro Pimentel-Coelho, Rosália Mendez-Otero, Gisele Zapata-Sudo
Journal: Circulation (2020)

Introduction: Right ventricle (RV) remodeling and vascular dysfunction are present in pulmonary arterial hypertension (PAH). Hypothesis: This work focuses on the benefits of the association of human umbilical cord mesenchymal stem cell (hMSC) with lodenafil, a PDE5 inhibitor, on PAH in rats. Methods: Experiments were in accordance with the Animal Care and Use Committee at the Federal University of Rio de Janeiro. PAH was induced in male Wistar rats by exposure to hypoxia (10% O 2 ) during 3 weeks plus i.p . injection of an antagonist of VEGF receptor (SU5416; 20 mg/kg/week). Animals were randomly divided (n=6): PAH + vehicle; PAH + lodenafil (gavage, 10 mg/kg); PAH + lodenafil + hMSC (5x10 5 , i.v.) for 14 days. Results: PAH induced the reduction of the ratio of pulmonary acceleration time and RV ejection time from 0.42 ± 0.01 to 0.24 ± 0.01, which was recovered to 0.31 ± 0.01 after treatment with lodenafil + hMSC. RV afterload confirmed by increased systolic pressure (mmHg) of 52.1 ± 8.8 (contro: 24.0 ± 3.1) was normalized to 29.6 ± 2.2 with association. Pulmonary arteries wall thickness (%) measured by immunohistochemistry for alpha-SMA was increased by HAP from 44.7 ± 1.4 to 64.2 ± 1.2 and was partial (57.7 ± 1.4) or totally recovered (47.3 ± 0.9) after treatment with lodenafil and association, respectively. Increased RV collagen fraction (%) of 7.4 ± 1.2 was induced by HAP when compared to control group (1.9 ± 0.1) and although lodenafil did not alter this parameter (6.6 ± 0.9) its association with hMSC restored to 2.7 ± 0.4. Increased RV wall thickness (mm) observed in PAH (from 0.60 ± 0.02 to 1.05 ± 0.13) recovered to 0.58 ± 0.04 after treatment with association. ERK1/2 expression evaluated by western blot analysis recovered from 0.79 ± 0.07 to 0.12 ± 0.06, which reinforced the reduction of cellular proliferation by treatment with lodenafil + hMSC. RV expression of p38 mitogen associated protein kinase was measured by stained area quantification using immunohistochemistry (%) was also increased in PAH group (from 9.4 ± 2.5 to 31.4 ± 2.2, p &lt; 0.05) and the association of lodenafil + hMSC reduced to 11.4 ± 3.4. Conclusions: Therapy of hMSC and lodenafil improved cardiac remodeling and vascular dysfunction in SuHx-PAH rats, representing an important approach for the future treatment of PAH.
Abstract 13614: Nck1 Regulates Endothelial Activation and Blood Brain Integrity After Ischemia Reperfusion Injury
Authors: Mabruka Alfaidi, Anthony W Orr
Journal: Circulation (2020)

Introduction: Stroke remains a leading cause of disease disability worldwide. Rapid restoration of blood flow after occlusion is required to minimize brain damage. However, with the reperfusion there is upregulation to oxidative stress pathways that stimulates interleukin-1 activates kinase type I (IRAK-1) within endothelial cells leading to proinflammatory genes expression (ICAM-1/VCAM-1). We previously showed that the Nck family of adaptor proteins promotes oxidative stress-induced inflammation following ischemia reperfusion (IRI). Nck1 and Nck2 are two highly similar proteins but have inherent functional differences. Hypothesis: We hypothesized that Nck1 is required for IRAK-1 activation in response to IRI. Methods: Human brain endothelial cells (ECs) were genetically silenced for Nck1, Nck2, or interleukin-1 receptor type I kinase-1 (IRAK-1) and exposed to hydrogen peroxide (exogenous oxidative stress) or hypoxia re-oxygenation (endogenous oxidative stress). Additionally, adult male mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) followed by 24h reperfusion. Neurological deficits were assessed using the 24 sensorimotor scoring system. Infarct volume, blood brain barrier (BBB) integrity, and brain inflammatory profiles were assessed using immunostaining and immunoblotting. Results: Knock down of endothelial Nck1 or Nck2 of cells markedly reduced VCAM-1 and ICAM-1 expression and NF-κB activation in response to H 2 O 2 and hypoxia re-oxygenation. In ECs treated with the proinflammatory mediator interleukin-1 (IL-1β), there was upregulation of IRAK-1 and NF-κB activation. However, deletion of Nck1, but not Nck2, significantly decreased IRAK-1/ NF-κB activation by IL-1β. Moreover, Nck1 inhibition decreased endothelial permeability-induced by oxidative stress. In response to oxidative stress, Nck1 directly binds to IRAK-1. Nck1 KO mice had significantly less infarct volume and neurological deficits after MCAO/reperfusion. BBB disruption measured by Evans Blue extravasation and Fibrinogen staining was remarkably reduced in Nck1 KO mice. Conclusions: Nck1 promotes ischemia/reperfusion-induced inflammation, and brain injury, therefore, Nck1 inhibition is a promising therapy to improve IRI.
Abstract 14675: Rising Prevalence of Obesity in the Us: National Health and Nutrition Examination Survey (NHANES) 2003-2018
Authors: michael palmer, Peter P Toth
Journal: Circulation (2020)

Introduction: Obesity is increasing globally. Obesity exacerbates risk for diabetes, dyslipidemia, hypertension, and ASCVD. We evaluated the prevalence of overweight and obese adults in the US during 2003-2018. HYPOTHESIS: The percentage of men and women overweight/obese is increasing continuously and may exceed the percentage with ‘normal’ weight. Methods: From 77007 participants in 8 NHANES surveys (between 2003-2004 and 2017-2018), we selected 39952 aged 20-79 years for this analysis. Participants with BMI data (n = 39440, 98.7%) were categorized as being underweight (BMI &lt; 18.5), normal (BMI 18.5 - &lt;25), overweight (BMI 25 - &lt;30), obese (BMI 30 - &lt;40) or morbidly obese (BMI 40+). Results were extrapolated to the entire US population (50 states plus the District of Columbia) using the direct method to the US Census 2000 population. Statistical analyses were performed in the R language. Results: There are statistically significant mean increases in BMI (95% confidence interval and p-value) between successive surveys of 0.18 (0.11, 0.25, p&lt;0.0001) for men and 0.24 (0.14, 0.33, p&lt;0.0001) for women. There are clear trends in morbid obesity (BMI 40+) from 3% in the first survey to 7% among men in the last survey, and from 7% to 12% in women. Obesity/morbid obesity (BMI 30+) increased from 31% to 44% in men and from 34% to 43% in women. About 78% of adult men are either overweight, obese, or morbidly obese (BMI 25+) in the most recent survey, an increase from 71% in the first survey. Among women 70% are either overweight, obese, or morbidly obese, an increase from 63% in the first survey. Very few US adults (1-2%) are underweight (BMI&lt;18.5). About one quarter of US adults have normal weight (BMI 18.5- 25). Conclusion: During the period 2003-2018, there has been a substantial rise among both US adult men and women in BMI who are overweight/obese. This necessitates invigorated public education about the clinical hazards posed and the need for lifestyle/dietary modification to stem this crisis.
Abstract 15988: Heart Failure Group Medical Visits to Improve Quality of Life: A Feasibility Study
Authors: Iniya Rajendran, Patricia Williams, Pei-Chun McGregor
Journal: Circulation (2020)

Introduction: Group Medical Visits (GMV) are medical appointments where patients with similar medical conditions are seen in a group setting. Heart Failure (HF) is an ideal fit for the GMV model of healthcare delivery. HF guidelines emphasize the need for a self-care regimen including symptom knowledge, medication adherence, dietary and lifestyle modifications and social support. We conducted an intervention with these elements in a GMV setting to assess feasibility and improvement in quality of life (QoL). Methods: We enrolled a convenience sample of high-risk veterans with HF who required frequent follow up. Veterans participated in a longitudinal GMV for eight sessions lasting two hours each and occurring once a month. A curriculum was prepared a priori, and each session was led by an invited guest facilitator and focused on nutrition, exercise, stress, holistic health among others. Feasibility was assessed through recruitment and retention data. We also collected pre-post medication compliance data and QoL change using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). We gathered feedback after each session. Results: Twelve patients were invited to the program and nine patients attended the first session. The average attendance was 6 participants each week with 4 participants attending all eight sessions. All were men, 22% identified as Black and 8 of 9 participants had preserved ejection fraction and obesity. At baseline, the mean KCCQ was 49.2. At the end of the intervention, the mean change in KCCQ-12 score was +9 (p=0.39). The largest change (+12, p=0.13) was seen on the QoL subscale. No significant improvement was seen in medication compliance. Participants listed community building, peer to peer education, learning about hospital services and continued contact with their provider as highlights of the program. Due to invitation of high-risk individuals, we had one death and seven hospitalizations during the study period. Conclusions: Longitudinal GMVs for high risk patients has a role in HF education and management. It may improve QoL and provider-patient relationship. It is well accepted by the veteran population and has the potential to be routinely integrated into clinical practice.
Abstract 15974: Non-Invasive Myocardial Work Indices in Normal Adolescents: A Pilot Study
Authors: Sarah Pradhan, Anna Mullikin, Vien T Truong, Wojciech Mazur, Michael D Taylor, Justin T Tretter
Journal: Circulation (2020)

Introduction: Myocardial work may provide a different perspective on LV function and energy consumption. Its non-invasive assessment by echocardiography correlates with invasive measures and there are normal values established in adult patients. We aimed to establish normal values in a healthy adolescent population. Methods: Nineteen healthy subjects (mean age = 15 ± 2 years, 42% male) with normal echocardiograms were prospectively included. Brachial cuff blood pressure was obtained immediately following apical images in the supine position. Post-processing of echocardiograms with speckle tracking echocardiography and derivation of global myocardial work indices from LV pressure-strain loops was done using EchoPAC (General Electric, v203R73.0) (Figure 1). Results: Baseline demographics, echocardiographic measures and global myocardial work indices are reported in Table 1. The mean global work index is 1833 ± 278 mmHg with mean global work efficiency of 95 ± 1.3%. No gender difference in myocardial work indices are found (p&gt;0.05 for all). Correlation between global work indices with age, systolic blood pressure, LV ejection fraction, and global longitudinal strain (GLS) are presented in Table 2. Conclusions: This is a pilot study to begin establishing normal adolescent indices of non-invasive myocardial work. Figure 1. Example