tbuckley/cabot-search huggingface dataset:
Evidence-Based Rationale for Use of Inferior Vena Cava Filters—Reply
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Alzheimer’s disease hypothesis and related therapies
Authors: Xiaoguang Du, Xinyi Wang, Meiyu Geng
Journal: Translational Neurodegeneration (2018)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies.
Long-Term Risk of Cardiovascular Disease in Women Who Have Had Infants With Heart Defects
Authors: Nathalie Auger, Brian J. Potter, Marianne Bilodeau-Bertrand, Gilles Paradis
Journal: Circulation (2018)

The possibility that congenital heart defects signal a familial predisposition to cardiovascular disease has not been investigated. We aimed to determine whether the risk of cardiovascular disorders later in life was higher for women who have had newborns with congenital heart defects.We studied a cohort of 1 084 251 women who had delivered infants between 1989 and 2013 in Quebec, Canada. We identified women whose infants had critical, noncritical, or no heart defects, and tracked the women over time for future hospitalizations for cardiovascular disease, with follow-up extending up to 25 years past pregnancy. We calculated the incidence of cardiovascular hospitalization per 1000 person-years, and used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for the association between infant heart defects and risk of maternal cardiovascular hospitalization. Models were adjusted for age, parity, preeclampsia, comorbidity, material deprivation, and time period.Women whose infants had heart defects had a higher overall incidence of cardiovascular hospitalization. There were 3.38 cardiovascular hospitalizations per 1000 person-years for those with critical defects (95% CI, 2.67-4.27), 3.19 for noncritical defects (95% CI, 2.96-3.45), and 2.42 for no heart defects (95% CI, 2.39-2.44). In comparison with no heart defects, women whose infants had critical defects had a hazard ratio of 1.43 (95% CI, 1.13-1.82) for any cardiovascular hospitalization, and women whose infants had noncritical defects had a hazard ratio of 1.24 (95% CI, 1.15-1.34), in adjusted models. Risks of specific causes of cardiovascular hospitalization, including myocardial infarction, heart failure, and other atherosclerotic disorders, were also greater for mothers of infants with congenital heart defects than with no defects.Women whose infants have congenital heart defects have a greater risk of cardiovascular hospitalization later in life. Congenital heart defects in offspring may be an early marker of predisposition to cardiovascular disease.
Abstract 15994: Inhibition of Nuclear Factor-κB mediated Inflammation Reverses Fibrosis and Improves Right Ventricular Function in Rats With Pulmonary Artery Banding
Authors: Keimei Yoshida, Kohtaro Abe, Keita Saku, Kenji Sunagawa
Journal: Circulation (2016)

Introduction:  In patients with pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction predicts poor prognosis. Although, nuclear factor-κB (NF-κB) is excessively activated in RV of PAH, how it affects RV function remains unknown. We hypothesized that the RV pressure overload activates NF-κB-mediated inflammation and deteriorates RV function.   Methods:  We banded the main pulmonary artery (PAB) using 18-gauge needle in Sprague-Dawley rats (BW: 180-220g). We evaluated hemodynamics and inflammatory responses of RV at Day1, 3, 7, 14 and 28 after PAB or sham operation (n=4-6, each group). We examined the effect of NF-κB inhibitor, pyrrolydine-dithiocarbamate (PDTC: 200mg/kg/day, dietary, Day -1 to 28 for prevention, Day14 to 28 for treatment, n=4-6, each group) on RV function and inflammation.   Results:  Comparing to sham, PAB of Day14 increased RV systolic pressure (78.6±5.2, vs. 31.1±3.3 mmHg, p 2 , p   Conclusions:  PAB activated NF-κB deteriorates RV function. The fact that PDTC reversed fibrosis and improved RV function indicates that the inhibition of NF-κB would be a novel therapeutic target for RV dysfunction in PAH
Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles
Authors: Annabelle Biscans, Reka A. Haraszti, Dimas Echeverria, Rachael Miller, Marie-Cecile Didiot, Mehran Nikan, Loic Roux, Neil Aronin, Anastasia Khvorova
Journal: Molecular Therapy (2018)

Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.
The Need for Neddylation: A Key to Achieving NED in Uveal Melanoma
Authors: Jessica Yang, Omid Hamid, Richard D. Carvajal
Journal: Clinical Cancer Research (2018)

The ability of uveal melanoma cells to enter and exit dormancy plays a fundamental role in the development of metastatic disease. Neddylation blockade is a promising strategy to prolong tumor dormancy via impaired angiogenesis and prevent the establishment of metastases via elimination of cancer stem-like cells. Clin Cancer Res; 24(15); 3477-9. ©2018 AACRSee related article by Jin et al., p. 3741.
Gordon E Anderson
Authors: David W Herring
Journal: BMJ (2018)

Gordon E Anderson was born in Aberdeen, the son of a medical biochemist at the Victoria Infirmary, Glasgow. He was initially schooled in Glasgow but returned to Aberdeen Grammar School as a boarder, during which time he developed an interest in engineering. At 18 he was diagnosed with tuberculosis, and during treatment he reconsidered his career plans. Excluded from national service he applied, successfully, for a place to read medicine at Glasgow Medical College. He graduated in 1964.

He started his specialist training in on obstetrics and gynaecology at Queen Mary’s Hospital in Glasgow under …
Abstract P193: High Density Lipoprotein is Superior to Triglyceride as a Biomarker of Physiologic Stress in African Immigrants: The Africans in America Study
Authors: Rafeal L Baker, Jean N Utumatwishima, Stephanie T Chung, Anne E Sumner
Journal: Circulation (2018)

Introduction: For Africans living in the United States, the extent to which stress-induced physiologic dysfunction varies by reason for immigration is unknown. Allostatic load score (ALS) is used to assess physiologic stress. ALS has biomarkers in 3 domains: cardiovascular, metabolic and immune. However, there are many ALS equations and the number of biomarkers in each domain varies. In the cardiac domain of ALS, equations use either triglyceride (TG) or high density lipoprotein (HDL). A specific problem for African descent populations is that HDL may be superior to TG as a marker of insulin resistance and cardiac risk. Objective: Our primary goal in 95 African immigrants (71% male, age 42±10, (mean±SD), range 22-62y) was to determine if ALS varied by reason for immigration. Our secondary goal was to evaluate 4 different ALS equations to determine if there was a difference in ALS performance depending on whether HDL or TG was the included biomarker. Methods and Results: For all 4 equations, the reasons for immigration from lowest to highest ALS were: family reunification, lottery for self and immediate family, marriage, asylum, work and study (Figure 1). As the first 3 reasons for immigration promoted family unity, they were grouped together (Group 1). The Africans who came for other reasons were grouped together (Group 2). Equations 1 and 2 included HDL as a biomarker. For these equations, ALS in Group 1 vs. Group 2 were: 1.7±1.3 vs. 2.8±1.7, P &lt;0.01 and 1.4±1.2 vs. 2.3±1.7, P &lt;0.01 resp. Equations 3 and 4 used TG. For these two equations ALS in Group 1 vs. Group 2 were: 2.2±1.6 vs. 2.9±2.0, P =0.08 and 2.1±1.4 vs. 2.9±2.0, P =0.03 resp. In Equations 1 and 2, when HDL was replaced by TG, the significant difference in ALS between groups declined. In Equations 3 and 4, when TG was replaced by HDL, the significant difference in ALS between groups increased. Conclusions: ALS varies by reason for immigration and is easier to detect in ALS equations which use HDL rather than TG.
Morbidity Versus Mortality
Authors: Johannes Clemmesen, Arne Nielsen
Journal: JNCI Journal of the National Cancer Institute (1982)

Morbidity Versus Mortality Get access Johannes Clemmesen, Johannes Clemmesen Stockholmsgade 43 Search for other works by this author on: Oxford Academic PubMed Google Scholar Arne Nielsen Arne Nielsen Institute of Human Genetics, Tagensvej 14 Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 3, September 1982, Page 549, https://doi.org/10.1093/jnci/69.3.549 Published: 01 September 1982
Abstract 11524: Preferential Use of Bare Metal Over Drug Eluting Stents in Primary Percutaneous Coronary Intervention: Can We Afford Current European Guidelines Recommendations?
Authors: Alberto Núñez García, Javier Botas Rodriguez, Luis A Inga Ayac, Roberto Del Castillo Medina, Lorenzo Hernando Marrupe, De la Rosa Riestra Adriana, Javier Alonso Bello, Maher Chichakli Cela
Journal: Circulation (2016)

DES reduce TLR risk compared to BMS in primary percutaneous coronary intervention (PPCI), with no benefit in mortality, and are currently recommended as first line therapy by the ESC guidelines. In the current era of budget constraints, proper selection of pts who may truly benefit from DES implantation is important. This study aims to evaluate the clinical outcomes of pts undergoing PPCI with a predetermined strategy of preferential use of BMS over DES. Methods: We retrospectively analyzed 283 consecutive STEMI pts (63±13 years) referred to our institution for PPCI (2007-2013). Hospital protocol recommended default BMS utilization, although it allowed DES implantation at operator’s discretion if the lesion was deemed to have a high restenosis risk. Pts were retrospectively allocated in three groups: Group 1 (n=112, 39.5%) BMS in lesions without a high restenosis risk, Group 2 (n=123, 43.5%) BMS in lesions with a high restenosis risk and Group 3 (n=48, 17%) DES implantation. Mean follow-up was 31± 19 months. Only 2 pts were lost to follow-up. Results: Pts in Groups 2 and 3 had a higher prevalence of diabetes, and pts in Group 3 had a higher prevalence of previous MI. Rates of death, myocardial infarction and stroke were similar among groups. TLR rate was higher in Group 2 (10.7%) vs. Group 1 (2.7%) and 3 (4.2%); p 0.03. Pts treated with BMS (Groups 1 and 2 combined) had a 6.8% TLR rate vs. 4.2% in pts treated with DES (Group 3, p=0.4). Although stent prizes vary among countries, estimating a cost of 500 $ per BMS and 1,000 $ for DES, the cost of a strategy of routine DES utilization in our cohort would have been 283,000 $ instead of the actual 165.500 $ (Δ 117.500 $, 41% savings). Even if only pts with low restenosis risk (Group 1) had been treated with BMS the cost would have been 227.000 $ (Δ 56.000 $ 19.7% savings). DES utilization in Group 1 might have reduced TLR rates but the low figure observed in our cohort (2.7%) indicates that this strategy may not be cost-effective. Conclusions: In pts undergoing PPCI, a strategy of preferential use of BMS showed excellent clinical results and led to important cost savings. In the current era of cost-effectiveness and budget restrictions BMS should be considered at least in pts with a priori low restenosis risk.
Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients
Authors: Michael T. Tetzlaff, Kelly C. Nelson, Adi Diab, Gregg A. Staerkel, Priyadharsini Nagarajan, Carlos A. Torres-Cabala, Beth A. Chasen, Jennifer A. Wargo, Victor G. Prieto, Rodabe N. Amaria, Jonathan L. Curry
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes. <h3>Case presentation</h3> We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57&nbsp;years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6&nbsp;months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5&nbsp;months since initiation of treatment. <h3>Conclusions</h3> The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.
Abstract 17358: The Determinants of Nonadherence to Long-term Medical Therapy in Post Myocardial Infarction
Authors: Yongwhi Park, Ki-Soo Park, Yong Whan Park, Young-Hoon Jeong, Jin Sin Koh, Jeong Rang Park, Choon Hwan Kwak, Jin Yong Hwang
Journal: Circulation (2013)

Background: Nonadherence to long-term therapies increases future events and health care costs in patients with myocardial infarction (MI). The aim of study was to search for the major determinants ...
Ending violence against children: a call to action
Authors: Shanti Raman, Tufail Muhammad, Jeffrey Goldhagen, Bernard Gerbaka, Nicholas J Spencer, Zulfiqar A Bhutta, Ayesha Kadir, Rajeev Seth, Catherine Maternowska, Bernard Gerbaka, Thea van Zeben-van der Aa, Susan Bennett, Susan Bissell, Ramya Subrahmanian, Tony Waterston, Danielle D'Annunzio
Journal: The Lancet Child & Adolescent Health (2018)
Interventions to Prevent Falls in Older Adults—Reply
Authors: Andrea C. Tricco, Sonia M. Thomas, Areti Angeliki Veroniki
Journal: JAMA (2018)

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
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution
Authors: Lei He, Hong-Xiang Zheng, Yanan Wang, Katherine Y. Le, Qian Liu, Jun Shang, Yingxin Dai, Hongwei Meng, Xing Wang, Tianming Li, Qianqian Gao, Juanxiu Qin, Huiying Lu, Michael Otto, Min Li
Journal: Genome Medicine (2018)

Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA. We used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs. We report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains. Our study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose.
A phase II trial of LEE011 in combination with everolimus in the treatment of advanced well differentiated neuroendocrine tumors of foregut origin.
Authors: Nitya Prabhakar Raj, Virginia Kelly, Jennifer A. Chan, A. Dasari, Marinela Capanu, Laura Tang, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2018)

TPS546 Background: Changes in the retinoblastoma (Rb) tumor suppressor pathway are believed to contribute to the development of well differentiated neuroendocrine tumors (WDNETs). In the pre-clinical setting, loss or downregulation of proteins that normally inhibit the cyclin dependent kinases Cdk4 and Cdk6 have contributed to NET development. Separately, rigorous investigation of everolimus in WDNETs has demonstrated a survival benefit in this patient (pt) population. Pre-clinical data suggests that the Cdk4/Cdk6 inhibitor LEE011 is synergistically active with everolimus. The aim of this study is to evaluate the efficacy and safety of LEE011 in combination with everolimus in pts with advanced WDNETs of foregut origin (thymic, bronchopulmonary, gastric, duodenal, pancreatic). Methods: This study is a multicenter, non-randomized, open-label phase II clinical trial using a Simon two stage optimal design. Main inclusion criteria include: adult patients with WDNET of foregut origin, low to intermediate grade, unresectable and/or metastatic, disease progression ≤ 12 months prior to enrollment, ECOG 0-1. Between 15 and 43 patients will be enrolled from three sites across the US. LEE011 300mg daily, 3 weeks on and 1 week off, in combination with everolimus 2.5mg daily (final dosing based on phase 1b clinical trial performed in metastatic breast cancer; LEE011X2106) will be administered orally until disease progression, unacceptable toxicity, investigator decision, or pt withdrawal. All enrolled pts will be followed by telephone contact for overall survival until death or consent withdrawal. The primary endpoint, progression free survival, will be assessed based on radiographic review by RECISTv1.1. Main secondary endpoints include establishing the safety of this drug combination in this patient population, objective response rate, clinical benefit rate, and overall survival. Correlative objectives include exploring the effect of this drug combination on biomarkers related to the Rb pathway and/or WDNET pathogenesis. This trial began enrollment in 2/27/2017, with 10 patients enrolled to date. Clinical trial information: NCT03070301.