tbuckley/cabot-search huggingface dataset:
Abstract 11913: Early Nonadherence With Dabigatran and Rivaroxaban in Patients With Atrial Fibrillation
Authors: Cynthia Jackevicius, Meytal Tsadok, Vidal Essebag, Clare Atzema, Mark J Eisenberg, Jack V Tu, Lingyun Lu, Elhame Rahme, Karin H Humphries, P. Michael Ho, Mintu Turakhia, Hassan Behlouli, Limei Zhou, Louise Pilote
Journal: Circulation (2015)

Background: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved recently for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring, and for dabigatran, dosing frequency may predispose patients to nonadherence. Limited information is available on the adherence rates and related clinical outcomes for dabigatran and rivaroxaban in clinical practice. Methods: We conducted a population-based cohort study using administrative data of patients aged 65 years and over with AF, linking hospital discharge abstract and prescription claims databases in Ontario, Canada from April 2012 to March 2014. Nonadherence was measured as proportion of patients discontinuing dabigatran or rivaroxaban, defined as a gap in dabigatran or rivaroxaban prescription for ≥14 days within the first 6 months of therapy, and time to discontinuation. A multivariate Cox proportional hazards model was used to examine the association between drug discontinuation at any time, and the composite outcome of hospitalization for stroke, or death. Results: The cohort consisted of 15,857 dabigatran users and 10,119 rivaroxaban users, with women comprising 52% of each medication group. Mean age was 80.7±6.7 years for dabigatran, and 77.0±7.1 years for rivaroxaban patients. At 6-months, 36.5% of patients discontinued dabigatran (110mg: 37.4%; 150mg: 34.1%), while 32.1% of patients discontinued rivaroxaban. Median time to discontinuation was 240 days (IQR: 78-523) for dabigatran and 140 days (IQR: 52-283) for rivaroxaban. Risk of the composite outcome (stroke or death) was significantly higher for those who discontinued dabigatran [HR 1.78 (95% CI 1.62-1.95);p&lt;0.0001] or discontinued rivaroxaban [HR 3.07 (95% CI 2.54-3.72);p&lt;0.0001] compared with those who did not discontinue the medication. Conclusions: Within 6 months of initiation, discontinuation rates are high in clinical practice, with 1 in 4 patients discontinuing dabigatran, and 1 in 3 patients discontinuing rivaroxaban. There is an association between nonadherence with either dabigatran or rivaroxaban and significantly worse clinical outcomes following medication discontinuation.
Fatal Hemorrhage in a Patient with an Acquired Inhibitor of Human Thrombin
Authors: Albert R. La Spada, Bjørn S. Skålhegg, Ruth Henderson, Gottfried Schmer, Robert Pierce, Wayne Chandler
Journal: New England Journal of Medicine (1995)

Thrombin (factor IIa) is a serine protease that performs a number of functions in blood coagulation.1 Among its most important actions is converting fibrinogen into fibrin monomers, which polymerize to form the fibrin clot. Thrombin participates in the activation of factors V, VIII, and XIII, as well as of platelets.2 By binding to thrombomodulin on vascular endothelial cells, it forms a complex that activates protein C, thereby limiting the extent of an emerging clot.3 Cleavage of thrombin's inactive zymogen precursor, prothrombin (factor II), is required to generate functionally active thrombin. Acquired inhibitors of certain coagulation factors are relatively common, but . . .
Low-pathogenicity<i>Mycoplasma</i>spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia
Authors: T J Nolan, N J Gadsby, T P Hellyer, K E Templeton, R McMullan, J P McKenna, J Rennie, C T Robb, T S Walsh, A G Rossi, A Conway Morris, A J Simpson
Journal: Thorax (2016)

<h3>Background</h3> Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function. <h3>Methods and setting</h3> 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at &gt;10<sup>4</sup> colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (<i>Mycoplasma</i> and <i>Ureaplasma</i> spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to <i>Mycoplasma salivarium</i> and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed. <h3>Results</h3> Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was <i>M. salivarium</i>. Blood monocytes from healthy volunteers incubated with <i>M. salivarium</i> displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to <i>M. salivarium</i> demonstrated impaired phagocytosis (p=0.005). <h3>Discussion and conclusions</h3> This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, <i>M. salivarium</i>, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.
Editorials and Conflicts of Interest
Authors: Marcia Angell, Jerome P. Kassirer
Journal: New England Journal of Medicine (1996)

In the August 29 issue of the Journal, we published an Original Article by Abenhaim et al., entitled “Appetite-Suppressant Drugs and the Risk of Primary Pulmonary Hypertension.”1 It dealt with the increased risk of primary pulmonary hypertension in subjects taking antiobesity drugs. In the same issue was a solicited editorial by Dr. JoAnn Manson and Dr. Gerald Faich, entitled “Pharmacotherapy for Obesity — Do the Benefits Outweigh the Risks?”2 As is the usual practice of the Journal, the editors asked the editorialists to put the study results into perspective for our readers. What we did not appreciate until it was . . .
Cannabis, Psychosis, and Mortality: A Cohort Study of 50,373 Swedish Men
Authors: Edison Manrique-Garcia, Antonio Ponce de Leon, Christina Dalman, Sven Andréasson, Peter Allebeck
Journal: American Journal of Psychiatry (2016)

Objective: The authors assessed 1) the overall risk of death among cannabis users compared with nonusers and the extent to which psychosis affects excess mortality; 2) mortality among persons with psychotic disorders and the extent to which cannabis use affects excess mortality; and 3) the interaction effect of cannabis use and diagnosis of psychotic disorders on mortality. Method: This was a longitudinal study of 50,373 Swedish male military conscripts (ages 18–19) who were followed in the National Cause of Death Register up to around age 60. Cox proportional hazard modeling was used to assess risk of death in relation to baseline cannabis use and diagnosis of psychotic disorders. Results: Subjects with a baseline history of heavy cannabis use had a significantly higher risk of death (hazard ratio=1.4, 95% CI=1.1, 1.8) than those without such a history. The authors found an excess mortality among subjects with psychotic disorders, but the level did not differ between those with a history of cannabis use (ever users: hazard ratio=3.8, 95% CI=2.8, 5.0; heavy users: hazard ratio=3.8, 95% CI=2.6, 6.2) and those without such a history (hazard ratio=3.7, 95% CI=3.1, 44). No interaction was observed between cannabis use and diagnosis of psychotic disorders with regard to mortality. Conclusions: The results suggest that individuals with an early history of heavy use of cannabis are at a higher risk of death than those with a history of no use of cannabis. Although the authors adjusted for several confounders at baseline, the results should be interpreted with caution because of a lack of information on confounders in the period after conscription.
Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis
Authors: Philipp Lurz, Christian Luecke, Ingo Eitel, Felix Föhrenbach, Clara Frank, Matthias Grothoff, Suzanne de Waha, Karl-Philipp Rommel, Julia Anna Lurz, Karin Klingel, Reinhard Kandolf, Gerhard Schuler, Holger Thiele, Matthias Gutberlet
Journal: Journal of the American College of Cardiology (2016)
Systemic Lupus Erythematosus and Pregnancy
Authors: Myron Garsenstein, Victor E. Pollak, Robert M. Kark
Journal: New England Journal of Medicine (1962)

AN understanding of the interrelations of pregnancy and systemic lupus erythematosus is of considerable clinical importance, particularly since the disease occurs most frequently in women during the reproductive age. The diagnosis has been facilitated by the description of the L.E.-cell phenomenon by Hargraves and his colleagues1 (1948). Thereafter, the clinical features became more widely recognized, and it became easier to differentiate systemic lupus erythematosus occurring in pregnancy from the other causes of toxemia of pregnancy.Although a number of isolated case reports have been documented2 3 4 5 6 7 8 9 10 11 12 13 14 we were able to find relatively few reports of larger series of pregnancies in patients . . .
Integrating POLST into Palliative Care Guidelines: A Paradigm Shift in Advance Care Planning in Oncology
Authors: Patricia A. Bomba, Daniel Vermilyea
Journal: Journal of the National Comprehensive Cancer Network (2006)

Because predicting and outlining guidance for all possible scenarios is difficult, advance directives are rarely sufficiently precise to dictate patient preferences in specific situations as a disease progresses. Nonetheless, advance care planning is an essential process that should begin at the time of diagnosis, if not already initiated, to ensure that all patient and family rights are preserved. Communicating effectively with the patient and family and having the patient designate a surrogate decision-maker are critical. Attention must be paid to resolving conflicts among patient values and preferences and those of family and the health care team. Patient-centered goals for care and expectations should be elicited at first assessment and reassessed frequently as conditions change. As a disease progresses, advance directives are rarely precise enough to predict all possible scenarios and outline guidance for care. Therefore, for patients with advanced metastatic cancer and a potential life expectancy of less than 1 year, converting patient-centered treatment goals into actionable medical orders while the patient maintains capacity is a more effective way to ensure that patient preferences are honored. Physician Orders for Life-Sustaining Treatment (POLST) and similar medical order forms provide explicit direction about resuscitation status (“code status”) if the patient is pulseless and apneic. POLST also includes directions about additional interventions the patient may or may not want. A decade of research in Oregon has proved that the POLST Paradigm Program more accurately conveys end-of-life preferences that are more likely to be followed by medical professionals than traditional advance directives alone.
Efficacy Analysis of Gefitinib +/- Ficlatuzumab in Serum Proteomic Based Subgroups of Patients with Previously Untreated Lung Adenocarcinoma
Authors: T.S.K. Mok, E. Tan, S.L. Greater, G. Chang, J.C. Yang, J. Gyuris, M. Han, P. Komarnitsky, F. Payumo, G. Pestano, J. Roder, D. Spinella, Z. Weng, K. Park
Journal: Annals of Oncology (2014)
148P: Concordance between detection of EGFR mutations on tissue and in circulating free tumor DNA (cftDNA) in newly diagnosed metastatic lung adenocarcinoma (mLA)
Authors: A. Veccia, O. Caffo, S. Girlando, S. Fasanella, M. Dipasquale, V. Murgia, M. Barbareschi, E. Galligioni
Journal: Journal of Thoracic Oncology (2016)
Intracellular Pathogenesis of Listeriosis
Authors: Frederick S. Southwick, Daniel L. Purich
Journal: New England Journal of Medicine (1996)

Listeria monocytogenes, an aerobic and facultatively anaerobic gram-positive bacillus, can be readily isolated from soil, dust, fertilizer, sewage, stream water, plants, and even processed foods stored at 4°C. The organism is also present in the intestinal tract of numerous mammals, birds, fish, and crustaceans. Recent epidemiologic studies provide strong evidence that both sporadic and common-source outbreaks of listeriosis are foodborne.1,2 Despite the pervasiveness of L. monocytogenes in the environment, the annual incidence of listeriosis is only 0.7 case per 100,000. However, the annual rate of infection is 3 times higher among persons over the age of 70 years . . .
Atherosclerosis in Chicken
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hypertensive Hypertrophic Cardiomyopathy of the Elderly
Authors: Eric J. Topol, Thomas A. Traill, Nicholas J. Fortuin
Journal: New England Journal of Medicine (1985)

Using echocardiography, we identified 21 patients with a syndrome that included severe concentric cardiac hypertrophy, a small left ventricular cavity, and supernormal indexes of systolic function without concurrent medical illness or ischemic heart disease. Thirteen of the patients presented with dyspnea or chest pain. All patients studied had a history of hypertension and were compared with normotensive controls matched for age and sex. The patients were elderly (mean age, 73.3 years), predominantly female (16 patients), and mostly black (15 patients). Their cardiac function was characterized by excessive left ventricular emptying (ejection fraction on two-dimensional echocardiography [patients vs. controls], 79±4 vs. 59±5 per cent, P<0.001) and abnormal diastolic function as manifested by a prolonged early diastolic filling period (279±25 vs. 160±45 msec, P<0.001) and reduced peak diastolic dimension increase (11±4 vs. 16±5 cm per second, P<0.05). In spite of the clinical presentation of heart failure, all of 9 patients receiving either beta-receptor antagonists or calcium-channel blocking agents obtained symptomatic relief, whereas 6 of 12 patients receiving vasodilator medications had severe hypotensive reactions, including one death. We conclude that this unique subset of hypertensive patients has a clinical syndrome that warrants recognition and tailored management. (N Engl J Med 1985; 312:277–83.)
Racial Differences in the Incidence of Cardiac Arrest and Subsequent Survival
Authors: Lance B. Becker, Ben H. Han, Peter M. Meyer, Fred A. Wright, Karin V. Rhodes, David W. Smith, John Barrett
Journal: New England Journal of Medicine (1993)

Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival.We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data.Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P < 0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services.The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables.
IMMU-130, a unique antibody-drug conjugate (ADC) of SN-38 targeting CEACAM5 antigen: Preclinical basis for clinical activity in metastatic colorectal cancer (mCRC).
Authors: Serengulam V. Govindan, Thomas M. Cardillo, Edmund A. Rossi, William J. McBride, Robert M. Sharkey, David M. Goldenberg
Journal: Journal of Clinical Oncology (2015)

625 Background: IMMU-130 is a CEACAM5-targeted ADC, labetuzumab-SN-38, with the drug being the active form of the topoisomerase I inhibitor, CPT-11, and substituted at 7-8 moles/mole of IgG. This agent is in phase I/II clinical trials in patients with relapsed mCRC (NCT01270698; NCT01605318). Methods: Therapy experiments were conducted in female athymic nude mice (n=5-10 per group), 4-6 weeks of age, bearing s.c. LS174T human colon carcinoma xenografts of ~0.2 cm 3 size, or 2 weeks after lung metastases were generated by i.v. injection of GW-39 human colon carcinoma cells. Untreated controls, including a non-targeting ADC, were included. Biodistribution was examined in the s.c model using a single 12.5-mg/kg dose of the ADC or unconjugated labetuzumab, each spiked with 111 In-labeled substrate. Tolerability studies were conducted in white New Zealand rabbits. Results: In the metastatic model, fractionated dosing of a total of 50 mg/kg of ADC showed that 2 × the schedules of twice-weekly × 2 weeks with 1 week off and once-weekly × 2 weeks with 1 week off doubled the median survival vs. untreated mice, and were better than a 25-mg/kg dose given on days 1 and 15 (p &lt; 0.0474; log-rank). Pre-dosing with as much as twice the dose of labetuzumab as the ADC dose in the metastatic model did not affect median survival (p &gt; 0.15). Therapy experiments in the s.c. model revealed that IMMU-130, with 50% of drug released in ~20 h, was superior to the conjugate with an ultrastable linker, that the ADC was better than an MTD of 5FU/leucovorin chemotherapy (p &lt; 0.0001), and that the ADC could be combined with bevacizumab for improved efficacy (p &lt; 0.031). Significantly better efficacy for the specific ADC vs. nonspecific ADC was observed. Pharmacokinetics in mice indicated ~25% longer half-life for the unconjugated MAb vs. ADC, but with minimal impact on tumor uptake. A tolerability study in rabbits showed the NOAEL to be the human equivalent dose of 40-60 mg/kg, given as two doses. Conclusions: Preclinical data show an excellent therapeutic window for IMMU-130, which appears to be translated into the clinical experience thus far. The potential for combination therapy is also indicated.
Domiciliary exhaled nitric oxide and eosinophilic airway inflammation in adults with asthma
Authors: Catriona Ruth Nanda, Amisha Singapuri, Marcia Soares, William Monteiro, Salman Siddiqui, Sherif Gonem
Journal: European Respiratory Journal (2016)

Sputum eosinophils are the gold standard measure of eosinophilic airway inflammation and there is strong evidence that titrating corticosteroid therapy to sputum eosinophils reduces the rate of asthma exacerbations [1]. However, this measurement is time consuming and requires specific technical expertise. Exhaled nitric oxide ( F eNO) is a noninvasive surrogate marker of eosinophilic airway inflammation that may be measured using small portable devices. Studies of using F eNO to titrate therapy have yielded mixed results [2, 3]. However, it is possible that one-off clinic readings may not be the best method of utilising F eNO, and the home monitoring potential of F eNO has not yet been fully explored. Exhaled nitric oxide home monitoring is a promising surrogate marker of eosinophilic airway inflammation in asthma <http://ow.ly/108ak4>
Abstract 3363: RAGE/S100A7/Stat3-axis enhances breast cancer growth and metastasis via modulating tumor microenvironment
Authors: Mohd W. Nasser, Nissar A. Wani, Janani Ravi, Grace A. Amponsah, Dinesh K. Ahirwar, Catherine A. Powell, Mohamad Elbaz, Helong Zhao, Konstantin Shilo, Ramesh K. Ganju
Journal: Cancer Research (2015)

Abstract The Receptor for Advanced Glycation Endproducts (RAGE), a multifunctional, multi-ligand receptor, has been shown to play an important role in inflammation. However, not much is known about its role in breast cancer growth and metastasis. In this report, we observed that RAGE expression is upregulated in triple negative breast cancer (TNBC) cell lines, primary tumors and lymph-node metastasis samples. RAGE-/- mice show reduced breast cancer growth. Additionally, blocking RAGE with neutralizing-antibody inhibited lung metastasis in an intracardiac mouse model. Further elucidation of RAGE-mediated mechanisms revealed that RAGE binds to S100A7 and mediates S100A7-induced cell migration, Stat3 and NF-ĸB activation. Our results also indicate that S100A7/RAGE axis-modulates invasion/migration through Stat3 dependent MMP9 activation. In addition, RAGE neutralizing antibody and soluble RAGE inhibited breast cancer progression and metastasis in the inducible mS100a7a15 mouse model system. We demonstrated that RAGE/S100A7 enhanced mammary hyperplasia, tumor growth and metastasis through Stat3 activation. Notably, our studies revealed that RAGE/mS100a7a15 modulates the breast tumor microenvironment through recruitment of phospho-Stat3/MMP9-positive tumor-associated macrophages. Our studies suggest that RAGE expression could be used as a novel biomarker for aggressive/invasive breast cancer, especially TNBC. Collectively, these findings suggest that RAGE/S100A7/Stat3-axis has a novel role in linking inflammation to the development of invasive/aggressive breast cancer including TNBC. Citation Format: Mohd W. Nasser, Nissar A. Wani, Janani Ravi, Grace A. Amponsah, Dinesh K. Ahirwar, Catherine A. Powell, Mohamad Elbaz, Helong Zhao, Konstantin Shilo, Ramesh K. Ganju. RAGE/S100A7/Stat3-axis enhances breast cancer growth and metastasis via modulating tumor microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3363. doi:10.1158/1538-7445.AM2015-3363