tbuckley/cabot-search huggingface dataset:
Abstract MP78: Effect of Beta-Blocker Therapy, Maximal Heart Rate and Exercise Capacity During Stress Testing on Long-Term Survival
Authors: Rupert K Hung, Mouaz Al-Mallah, Seamus P Whelton, Roger S Blumenthal, Clinton A Brawner, Steven J Keteyian, Michael J Blaha
Journal: Circulation (2015)

Background: Whether beta-blocker therapy (BBT) attenuates the prognostic value of percentage-predicted maximal heart rate (ppMHR) achieved during stress testing remains unclear. The combined effect of ppMHR and exercise capacity on long-term mortality is unknown. Methods: We analyzed 67,772 adults (54 ± 13 years old, 54% men (36,639 of 67,772), 29% black (19,834 of 67,772)) from The FIT Project, a retrospective cohort study of patients who underwent physician-referred exercise stress testing at a single healthcare system between 1991 and 2009. Patients were categorized by baseline use of BBT. Maximal age-predicted heart rate was defined as 220-age. We derived adjusted mortality rates over the range of ppMHR using margins of response logistic regression models. Our primary model included adjustment for demographic data, resting blood pressures, medical history, pertinent medications, and indication for stress testing. Our secondary model included further adjustment for exercise capacity. Results: There were 10,594 deaths over 11 ± 5 years of follow-up. Patients on BBT tended to have more comorbidities and other medication use (P&lt;.001). After accounting for differences between BBT groups, BBT was associated with an 8% lower ppMHR (83% in BBT vs. 91% in no BBT) in both men and women. ppMHR was inversely associated with all-cause mortality in both analyses performed (P≤.001), though the association was significantly attenuated by BBT (P=.03) [Panel A]. Exercise capacity further attenuated the prognostic value of ppMHR in all patients, particularly in those on BBT, and reduced the difference in risk between those on BBT and not on BBT (P=.08) [Panel B]. Conclusion: BBT attenuated the association between ppMHR achieved during stress testing and long-term mortality. Exercise capacity further attenuated the prognostic significance of ppMHR, particularly in patients on BBT.
Safety of Ximelagatran
Authors: Allen Brinker, Ruyi He, Mehul Desai, Kate Gelperin, Kathy Robie-Suh
Journal: JAMA (2005)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract 1184: Urban Particulate Matter Air Pollution is Associated With Subclinical Atherosclerosis: Results From the Heinz Nixdorf Recall Study
Authors: Barbara Hoffmann, Marcus Bauer, Susanne Moebus, Stefan Mohlenkamp, Nico Dragano, Christoph Kessler, Hermann Jakobs, Raimund Erbel, Karl-Heinz Jockel
Journal: Circulation (2009)
A Phase I Study Of An Anti-CD30 x Anti-CD16A Bispecific Tandab Antibody, AFM13, In Patients With Relapsed Or Refractory Hodgkin Lymphoma
Authors: Eugene Zhukovsky, Achim Rothe, Bastian von Tresckow, Max Topp, Anas Younes, Dennis A. Eichenauer, Horst Hummel, Katrin S. Reiners, Markus Dietlein, Joerg Kessler, Miroslav Ravic, Christian Hucke, Elke Poggevon Strandmann, Andreas Engert
Journal: Blood (2013)
Prognostic significance of a positive microscopic margin in high-risk extremity soft tissue sarcoma: implications for management.
Authors: M J Heslin, J Woodruff, M F Brennan
Journal: Journal of Clinical Oncology (1996)

A positive microscopic margin (PMM) is a significant prognostic variable and leads to local recurrence (LR) in high-grade soft tissue sarcoma (STS) patients. Its effect on the rate of distant metastasis (DM) and tumor mortality (TM) remains controversial.One hundred sixty-eight primary, high-risk (high-grade, deep, > or = 5 cm) extremity STS patients were identified from our data base, of which 42 had a PMM. Limb-sparing surgery (LSS) was the primary surgical therapy in 144 patients; 24 received amputation (AMP). Statistical analysis was by log-rank test and Cox model. Significance was defined as a P value less than .05.A PMM was a significant negative prognostic factor for both DM and TM (P = .002 and .002, respectively). However, those patients who received LSS with 28% PMMs showed no significant difference in the rate of DM or TM compared with patients who received AMP with only 8% PMMs (log-rank, P = .057 and .28, respectively). A PMM was significantly associated with > or = 1,000 mL blood loss and more than 3 hours of operating time (P < .006 and .001, respectively).The strong statistical significance that relates a PMM to DM and TM in high-risk STS of the extremity is likely related to biologically aggressive tumors and LSS. Residual microscopic disease is not a guarantee of LR. The main problem in this group of patients is not LR, but DM and subsequent death. Therefore, to increase a disability with further surgery or amputate a patient's limb without clear evidence of LR in this group at high risk for distant recurrence is not recommended.
Abstract P204: Joint Association Between Birth Weight At Term And Later Life Adherence To A Healthy Lifestyle With Risk Of Hypertension
Authors: Yanping Li, Sylvia H Ley, Tyler J VanderWeele, Gary C Curhan, Janet W Rich-Edwards, Willett C Walter, John P Forman, Frank B Hu, Lu Qi
Journal: Circulation (2015)

Objective:  to prospectively assesse the joint association between birth weight and established lifestyle risk factors in adulthood with incident hypertension, and to quantity decompose the attributing effects to birth weight only, to adulthood lifestyle only and to their interaction.   Methods:  We followed 52,114 women from the Nurses9 Health Study II without hypercholesterolemia, diabetes, cardiovascular disease, cancer, prehypertension and hypertension at baseline (1991-2011). Women born preterm, of a multiple pregnancy, or who were missing birth weight data were excluded. Unhealthy adulthood lifestyle was defined by compiling status scores of body mass index (BMI), physical activity, alcohol consumption, the Dietary Approaches to Stop Hypertension (DASH) diet, and the use of nonnarcotic analgesics.   Results:  We documented 12,588 incident cases of hypertension during 20 years of follow-up. The risk of hypertension associated with a combination of low birth weight at term and unhealthy lifestyle factors (RR 1.95; 95%CI: 1.83-2.07) was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale ( P  interaction    Conclusion:  Our findings suggest that a combination of a healthy birth weight and a healthy adulthood lifestyle could prevent 66% of the cases of hypertension in this population, and the combined effects of lower birth weight at term and unhealthy lifestyle with the risk of hypertension are greater than additive.
Acute cardiomyopathy in rheumatoid associated lung disease
Authors: Ari Manuel, Tom Vale, Chris Turnbull, Colm McCabe, Norman Qureshi, Annabel Nickol
Journal: European Respiratory Journal (2011)

A 67 year old lady with rheumatoid arthritis on prednisolone, methotrexate and hydroxychloroquine was admitted with chest pains, breathlessness and blood stained sputum. She had a history of obliterative bronchiolitis and bronchiectasis secondary to rheumatoid, previously treated with cyclophosphamide and Rituximab immunosuppression.  An ECG at presentation showed T wave inversion in the anteroseptal leads. Subsequent Troponin I was positive. CT pulmonary angiography revealed no evidence of PE. Antiplatelet agents were commenced. Serial ECGs showed dynamic changes and the patient underwent urgent coronary angiography, which revealed entirely normal coronary arteries but an abnormal left ventriculography.  There was marked LV apical hypokinesis and ballooning. Cardiac MRI supported the suspicion of Takutsubo9s cardiomyopathy.   Discussion:  Takutsubo9s cardiomyopathy is a cause of cardiac chest pain and troponin release, accounting for up to 2% of ST-elevation myocardial infarction (MI). To our knowledge Takutsubo9s is undescribed in patients with rheumatoid bronchiolitis obliterans and bronchiectasis. The similarity in presentation to MI and pulmonary embolism creates diagnostic confusion.Whether the lung inflammation associated with rheumatoid confers an additional risk for Takutsubo9s remains unknown. This diagnosis therefore warrants consideration as unnecessary anticoagulation and antiplatelet therapies may have dangerous sequelae.
Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia?
Authors: STEPHEN M. LAWRIE, BAYANNE OLABI, JEREMY HALL, ANDREW M. McINTOSH
Journal: World Psychiatry (2011)

A diagnosis of schizophrenia, as in most of psychiatric practice, is made largely by eliciting symptoms with reference to subjective, albeit operationalized, criteria. This diagnosis then provides some rationale for management. Objective diagnostic and therapeutic tests are much more desirable, provided they are reliably measured and interpreted. Definite advances have been made in our understanding of schizophrenia in recent decades, but there has been little consideration of how this information could be used in clinical practice. We review here the potential utility of the strongest and best replicated risk factors for and manifestations of schizophrenia within clinical, epidemiological, cognitive, blood biomarker and neuroimaging domains. We place particular emphasis on the sensitivity, specificity and predictive power of pathophysiological indices for making a diagnosis, establishing an early diagnosis or predicting treatment response in schizophrenia. We conclude that a number of measures currently available have the potential to increase the rigour of clinical assessments in schizophrenia. We propose that the time has come to more fully evaluate these and other well replicated abnormalities as objective potential diagnostic and prognostic guides, and to steer future clinical, therapeutic and nosological research in this direction.
Adaptive T‐cell responses regulating oral tolerance to protein antigen
Authors: M. F. du Pré, J. N. Samsom
Journal: Allergy (2010)

To cite this article: du Pré MF, Samsom JN. Adaptive T‐cell responses regulating oral tolerance to protein antigen. Allergy 2011; 66 : 478–490. Abstract The term oral (or mucosal) tolerance has been classically defined as the suppression of T‐ and B‐cell responses to an antigen by prior administration of the antigen by the oral route. In recent years, it has become clear that both innate and acquired regulatory immune responses are essential for the development of oral tolerance. As such, mucosal microenvironmental factors such as transforming growth factor‐ β, prostaglandins but also dietary vitamin A create conditioning of an adaptive regulatory T‐cell response that suppresses subsequent antigen‐specific responses. Particular resident subsets of antigen presenting dendritic cells are pivotal to convey conditioning signals next to the presentation of antigen. This review discusses the primary mechanisms of adaptive regulatory T‐cell induction to ingested soluble protein antigen. However, we also discuss the limitations of our knowledge with respect to understanding the very common food hypersensitivity Celiac disease caused by an aberrant adaptive immune response to the food protein gluten.
Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long‐Term Treatment Response in Rheumatoid Arthritis
Authors: Meghna Jani, Hector Chinoy, Richard B. Warren, Christopher E. M. Griffiths, Darren Plant, Bo Fu, Ann W. Morgan, Anthony G. Wilson, John D. Isaacs, KimmeL. Hyrich, Anne Barton
Journal: Arthritis & Rheumatology (2015)

Objective To investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions. Methods A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated. Results Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m 2 and poor adherence were associated with lower drug levels. Conclusion Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.
Facial thermography is a sensitive and specific method for assessing food challenge outcome
Authors: A. T. Clark, J. S. Mangat, S. S. Tay, Y. King, C. J. Monk, P. A. White, P. W. Ewan
Journal: Allergy (2007)

Background: Oral challenge is widely used for diagnosing food allergy but variable interpretation of subjective symptoms may cause error. Facial thermography was evaluated as a novel, objective and sensitive indicator of challenge outcome. Methods: A total of 24 children with a history of egg allergy underwent oral challenge, which were scored positive when objective symptoms occurred or negative after all doses were consumed without reaction. Facial temperatures were recorded at baseline and 10‐min intervals. The difference between mean and baseline temperature (ΔT), maximum ΔT during challenge (ΔT max ) and area under curve of ΔT against time (ΔTAUC) were calculated for predefined nasal, oral and forehead areas, and related to objective challenge outcome. Results: There were 13 positive and 11 negative challenges. Median nasal ΔTAUC and ΔT max were greater in positive compared with negative challenges (231‐ and 5‐fold, respectively; P &lt; 0.05). In positive challenges, nasal temperatures showed an early transient rise at 20 min, preceding objective symptoms at median 67 min. There was a sustained temperature increase from 60 min, which was reduced by antihistamines. A cut‐off for nasal ΔT max of 0.8°C occurring within 20 min of the start of the challenge predicted outcome with 91% sensitivity (positive predictive value [PPV] 100%) and 100% specificity (negative predictive value [NPV] 93%). Subjective symptoms occurred in four of 13 positive and three of 11 negative challenges. Conclusions: Facial thermography consistently detects a significant early rise in nasal temperature during positive compared with negative food challenges, which is evident before objective symptoms occur. Thermography may therefore provide a sensitive method to determine outcome of food challenges and investigate the pathophysiology of food allergic reactions.
Abstract 10923: Myocardial Perfusion Reserve Measured by Adenosine Stress Magnetic Resonance Imaging in Systemic Lupus Erythematosus Patients with Angina but No Coronary Artery Disease
Authors: Pavel Goykhman, Louise E Thomson, Daniel S Berman, YuChing C Yang, Leslee Shaw, Mariko Ishimori, Rebecca Martin, Daniel J Wallace, Jay N Schapira, Rory Hachamovitch, Chrisandra L Shufelt, Michael H Weisman, C. Noel Bairey Merz
Journal: Circulation (2010)

Background: We have previously demonstrated that visually assessed adenosine stress perfusion cardiac magnetic resonance imaging (CMRI) is frequently abnormal in patients with Systemic Lupus Erythematosus (SLE) and symptoms of angina in the absence of obstructive coronary artery disease (CAD). Objectives CMRI measures including quantitative assessment myocardial perfusion reserve index (MPRI) have not been evaluated in this setting.

Methods: CMRI at 1.5 Tesla was performed in 18 women (age 41.4±10.5 years) with low to moderate SLE disease activity index (SLEDAI) and angina but no obstructive CAD by computed tomography, and in 10 asymptomatic reference control group women (mean age 53.2±5 years, p=0.001). CMRI was performed using a standardized protocol with 0.05mmol/kg gadolinium adenosine stress followed by rest perfusion imaging in three short axis slices. First pass perfusion images where analyzed in whole, subepicardial and subendocardial regions by PIE medical software (Netherlands). MPRI was calculated as the ratio of stress/rest relative upslope, corrected for left ventricular input. Univariate and multivariate linear analysis were performed.

Results: All patients and controls had normal cardiac structure and left ventricular systolic function. Mean MPRI in patients versus controls was reduced in all three myocardial regions (Table1). Multivariate linear regression revealed that the presence of SLE was the only predictor of subepicardial (p<0.0025, β:-1.059) and subendocardial (p<0.05, β:-0.529) MPRI.

Conclusion: Among SLE patients with angina but no obstructive CAD, reduced MPRI measured by CMRI is observed compared to controls, and SLE predicts abnormal MPRI. These findings suggest that further investigation is warranted in this population to test the hypothesis that angina in SLE patients but no obstructive CAD is due to myocardial ischemia related to microvascular coronary dysfunction.

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871. Long-Term Expression of Sleeping Beauty Transposon in the Murine Model of Mucopolysaccharidosis (MPS) Type VII
Authors: Audrey Arfi, Christophe Bourgoin, Luisa Basso, Sandro Sonnino, Livia Poenaru, Catherine Caillaud
Journal: Molecular Therapy (2004)

Sandhoff disease is an autosomal recessive neurodegenerative disease characterized by the intralysosomal accumulation of GM2 ganglioside. It is due to mutations in the hexosaminidases β-chain gene, resulting in a hexosaminidases A (αβ) and B (ββ) deficiency. This neurolipidosis, characterized by a predominant involvement of the central nervous system, has a dramatic evolution leading to early death. There is no efficient treatment for GM2 gangliosidosis to date.
Angioplasty shows better long term results than drug treatment
Authors: Scott Gottlieb
Journal: BMJ (1999)

<h3>Abstract</h3> The host epigenetic landscape is rapidly changed during SARS-CoV-2 infection and evidence suggests that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation changes in immune cells and alterations to epigenetic clocks in blood relate to severe COVID-19. However, a longitudinal assessment of DNA methylation states and epigenetic clocks in blood from healthy individuals prior to and following test-confirmed non-hospitalized COVID-19 has not been performed. Moreover, the impact of mRNA COVID-19 vaccines upon the host epigenome remains understudied. Here, we first examined DNA methylation states in blood of 21 participants prior to and following test confirmed COVID-19 diagnosis at a median timeframe of 8.35 weeks. 261 CpGs were identified as differentially methylated following COVID-19 diagnosis in blood at an FDR adjusted P value &lt;0.05. These CpGs were enriched in gene body and northern and southern shelf regions of genes involved in metabolic pathways. Integrative analysis revealed overlap among genes identified in transcriptional SARS-CoV-2 infection datasets. Principal component-based epigenetic clock estimates of PhenoAge and GrimAge significantly increased in people over 50 following infection by an average of 2.1 and 0.84 years. In contrast, PCPhenoAge significantly decreased in people under 50 following infection by an average of 2.06 years. This observed divergence in epigenetic clocks following COVID-19 was related to age and immune cell-type compositional changes in CD4+ T cells, B cells, granulocytes, plasmablasts, exhausted T cells, and naïve T cells. Complementary longitudinal epigenetic clock analyses of 36 participants prior to and following Pfizer and Moderna mRNA-based COVID-19 vaccination revealed vaccination significantly reduced principal component-based Horvath epigenetic clock estimates in people over 50 by an average of 3.91 years for those that received Moderna. This reduction in epigenetic clock estimates was significantly related to chronological age and immune cell-type compositional changes in B cells and plasmablasts pre- and post-vaccination. These findings suggest the potential utility of epigenetic clocks as a biomarker of COVID-19 vaccine responses. Future research will need to unravel the significance and durability of short-term changes in epigenetic age related to COVID-19 exposure and mRNA vaccination.