tbuckley/cabot-search huggingface dataset:
Investigators have a duty to minimise waste in pragmatic trials
Authors: Stephen J Chapman, James C D Glasbey
Journal: BMJ (2017)

Campbell, Weijer, and colleagues debate the duty to take part in pragmatic randomised trials.1 Randomised controlled trials in surgery are frequently pragmatic because of unique challenges related to complex interventions. Although once described as “comic opera,” surgical research in the UK has advanced significantly in recent years owing to dedicated surgical …
Abstract 166: Interaction Between LDL and Sympathetic Adrenoreceptors
Authors: Daniel Grün, Janna Lendner, Stephan Krohn, Agnes Jumar, Andreas Zakrzewicz, Eugeny Ermilov, Günter Siegel
Journal: Circulation Research (2012)

Introduction: LDL is a significant risk factor for cardiovascular disease and is known to impair flow-dependent vasodilatation. Furthermore, it has been demonstrated that LDL can even directly cause vasoconstricton. Recent studies suggested that lower LDL levels, achieved through administration of statins, are correlated with lower blood pressure, independent from pleiotropic statin effects. Our objective was to investigate whether LDL-induced impairment in flow-dilatation was due to an interaction of LDL with sympathetic adrenoreceptors. Materials and Methods: Flow-dependent isometric tension, intracellularly recorded membrane potential and cAMP-cGMP were measured in segments of 22 coronaries from heart transplantations. Results: As compared to Krebs solution, LDL affected flow-dilatation and caused a relative contraction [Δ(T 3 -T 100 ): Krebs 0.459 g; LDL 0.278 g]. Complete blockade of both α- (phentolamine 10 -7 mol/L) and β-receptors (propranolol 10 -7 mol/L) resulted in a ∼50% reduction of flow-dilatation impairment induced by LDL. Blockage of either α- (1) or β-receptors (2) showed smaller effects which added up to the measured effect under blockade of both receptors (4). Similar effects were apparent in the recorded membrane potential of the vascular smooth muscle cells. Discussion: We conclude that the LDL-induced impairment in flow-dependent dilatation is partially due to the interaction between lipoprotein and both α- and β-adrenoreceptors. Since blockade of each receptor resulted in a relative dilatation, we assume that the LDL effect is caused by a stimulation of α-adrenoreceptors and an inhibition of β-adrenoreceptors.
AB0767 Il-17-22-23 pathways in psoriatic arthritis and psoriasis
Authors: K Nas, R Cevik, I Yildiz, J Rech, G Schett
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy-associated with psoriasis. T helper 17 pathway has been shown to play an important role in PsA. <h3>Objectives</h3> In this study, we aimed to investigate concentrations of TH17 pathway cytokines such as IL-17, IL-22 and IL-23 in psoriasis (PsO) with/and without structural bone damage and psoriatic arthritis (PsA), and their relationship with disease activity and clinical findings. <h3>Methods</h3> A total number of 74 patients, 24 patients with PsA (mean age 57.5±11.37; 13 women, 11 men) and 25 patients with PsO and structural bone damage (mean age 49±13.92; 11 women, 14 men) and 25 patients with PsO and no structural bone damage (mean age 41±16.77; 7 women, 18 men), were recruited from the Department Internal Medicine 3 of the University of Erlangen-Numberg. Both PsO and PsA patients were evaluated according to the CASPAR criteria. Demographic and disease specific variables were recorded. Bone architecture of the metacarpal heads II and III were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT, Scanco, Switzerland). Disease activity was assessed with Disease Activity Score (DAS28). Psoriatic skin and nail disease activity were measured by the PASI. <h3>Results</h3> The ages of the patients in the three groups were similar. <i>IL-17A concentrations were significantly differed between the</i> groups (p=0.000). However, for other cytokines there was no difference between PsA and PsO groups. Serum levels of IL-17A were significantly correlated to patient pain of VAS (r=-0.318, p=0.06), VAS patient global assessment (r=0.272, p=0.021), DAS28 (r=-0.394, p=0.001) and PASI (r=0.519, p=0.000) in PsA and PSO. PASI score were also positively correlated with IL23 (r=-0.286, p=0.015) and S100A8 (r=0.298, p=0.011). <h3>Conclusions</h3> IL-17A seems to play an important role in development of PsA and bone damage in PsO. This role should be elucidated by further and larger clinical studies. <h3>Disclosure of Interest</h3> None declared
Scrotal Ulceration and Pyrexia
Authors: Catherine C. Foley, Pauline Marren
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
Annual Review of Microbiology. Volume 37.
Journal: Annals of Internal Medicine (1983)

In this volume the custom of publishing critical reviews of the current literature is continued. The virologist will find excellent summaries on the developmental stages of viruses, the biochemical aspects of viral growth, and the ecology of mosquitoborne viruses. In addition, a chapter on viral and rickettsial toxins is included. Of interest to the parasitologist are discussions on amebiasis, the morphology of protozoa, and the metabolism, nutrition, and chemotherapy of helminths. The subject of medical mycology is introduced here for the first time. The soil as an important reservoir of pathogenic fungi and the correlation between climatological conditions and the incidence of fungous infections are among the topics discussed. In the field of bacteriology, reviews on the following subjects are presented: acid-fast bacteria, genetics of micro-organisms, biological nitrogen fixation, food poisoning, and the microbiology of water and sewage. The production of antibiotics, alcohols, organic acids, vitamins, bacterial polysaccharides, and enzymes
PCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes
Authors: Connie N. Hess, Cecilia C. Low Wang, William R. Hiatt
Journal: Annual Review of Medicine (2017)

Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of low-density lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia. In addition, adverse effects of statins may limit their tolerability and therefore the ability to attain effective doses in some patients. A new class of drugs that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed to treat hyperlipidemia. This review discusses the history and mechanism of action of PCSK9 inhibitors, their metabolic effects, and clinical outcomes associated with these medications, highlighting recent large cardiovascular outcome trials investigating these therapies.
Abstract 159: New Insight of Coronary Wall Structural Changes from an Optical Coherence Tomography (OCT) study Following Kawasaki Disease.
Authors: Nagib Dahdah, Audrey Dionne, Ragui Ibrahim, Catherine Gebhard, Anne Fournier
Journal: Circulation (2015)

Background: Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease (KD). Coronary imaging usually describes aneurysms, stenosis and dilatation. Optical coherence tomography (OCT) is a technique useful for intracoronary imaging and coronary wall structure characterization. Method: KD patients scheduled for routine coronary angiography underwent OCT imaging between June 2013 and August 2014. Subjects’ clinical courses with echocardiography and angiography were reviewed to contrast with OCT findings. Results: OCT was performed on 18 patients 9.0 ± 5.1 years after KD at 12.4 ± 5.5 yo (range 3.5-21 yo). Of those, 14 (77.7%) had a history of CAA (7 giant CAA, 7 regressed CAA at time of OCT). Prophylactic intracoronary nitroglycerin was given (88.4 ± 45.5 μg/m2). Total X-ray exposure was 10.9 mGy/kg. One patient had a transitory uneventful vasospasm at the site of a former CAA, otherwise no major complications occurred (such as dissection, thrombosis, ischemia, arrhythmia). OCT findings were intimal hyperplasia in 15/18 (83.3%) on aneurysmal and regressed aneurysm segments. Intimal hyperplasia measured 390.8 ± 166.0 μm for the affected segments, compared to 61.7 ± 17.0 μm for the unaffected segments (p&lt;0.001). Destroyed media, fibrosis, calcifications, macrophage infiltration, neovascularization and white thrombus were also seen (Table 1). In two cases with previously implanted stent, the neo-intima was identified, measuring 80-160 μm. Conclusion: In our experience, OCT proved safe and insightful in the setting of KD. The observed coronary structural changes correspond to histological findings described in the literature late after KD.
Does a personalized multifaceted care plan (PMCP) improve quality of care?
Authors: Rashida Haq, Julia Rackal, Christine B. Brezden, Ralph George, Jory Simpson, Ronita Lee, Fok Han Leung, Kathy Vu, Suzanne Richter, Tara Jainudeen, Aleksandra Jovicic, Amy Kong
Journal: Journal of Clinical Oncology (2015)

e17663 Background: Breast cancer (BC) is the most frequently diagnosed cancer in women in North America. Institute of Medicine (2005) recommended that principal providers of oncology treatment provide patients with a care plan. Our earlier study showed that “one size does not fit all” and care plans need to be personalized (Haq et al., 2013). In this study, a Personalized Multifaceted Care Plan (PMCP) was developed and evaluated. Methods: A mixed methods design was used in this randomized controlled study. A total of 72 women diagnosed with invasive BC and expected to undergo neoadjuvant/adjuvant treatments were recruited from the multidisciplinary breast clinic. Participants were randomized to the control or intervention group, and stratified to chemotherapy versus endocrine therapy. The PMCP(intervention) included patients’ breast pathology, recommended treatment and follow-up care plans, and access to the study website. Quantitative outcomes were assessed through quality of life (Edmonton Symptom Assessment System-revised) and quality of care (Patient Satisfaction with Cancer Care, and Communication and Attitudinal Self Efficacy scale for Cancer) questionnaires that patients completed before and after chemotherapy treatment. Baseline and post-intervention questionnaire scores are compared among the control and intervention groups, and across treatments using unpaired t-tests. After completion of treatment, qualitative analysis was conducted in the intervention group, using patient focus groups and primary care provider (PCP) interviews. Results: Qualitative: 17 of the 18 focus group participants found that the PMCP helped them feel ‘educated’ about their cancer treatment. As one person described, “knowledge is power” and the PMCP “changes the level of knowledge and involvement you feel you have”. PCPs found the PMCP contained useful, concise medical summaries. Quantitative: Post-intervention quality of care scores increased in the intervention group but was unchanged in the control group. Further findings will be presented at the conference. Conclusions: PMCP appears to improve quality of care. Qualitative findings indicate the PMCP provide useful information to educate patients and assist PCPs in caring for them.
Reply to Voelkel: Cigarette Smoke Is an Endothelial Cell Toxin
Authors: Francesca Polverino, Bartolome R. Celli, Caroline A. Owen
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The report by Polverino and colleagues (1) provides a wonderful example of productive interdisciplinary collaboration.The authors connect lung and kidney endothelial cell damage and cigarette smoke in patients with chronic obstructive pulmonary disease and in smoke-exposed mice.This is an important study with far-reaching implications.Mechanistically, the authors point to generation of advanced glycation end products and receptor for advanced glycation end products activation triggered by oxidant stress, yet there are likely additional mechanisms that can be considered.Because the kidneys do not inhale, it is evident that it is the "circulating cigarette smoke" that is toxic to endothelial cells.For example, one component of cigarette smoke is the highly aggressive aldehyde acrolein (2-4), which can be measured in the blood and urine of smokers.A large number of experimental studies leave no doubt that cigarette smoke extract injures cultured endothelial cells.These findings have been frequently ignored or characterized as clinically irrelevant, yet they provide mechanistic insights and allow us to consider the hypothesis that emphysema is a vascular problem (5).If the notion that cigarette smoke cannot cross the alveolarcapillary barrier is dismissed, the fact that components of cigarette smoke are circulating has been firmly established.Although cigarette smoke extract in vitro kills endothelial cells directly, in vivo cigarette smoke components could, in susceptible individuals, trigger an immune response that includes the production of antiendothelial antibodies (6).Another implication of the findings published by Polverino and colleagues is that not only are the lung and kidney microvessels affected by cigarette smoke components but similarly the microcirculation of the skeletal muscles, the myocardium, and the retina are affected (1).Interesting correlations, not provided by the authors, are those between albuminuria and the diffusing capacity of the lung for carbon monoxide and albuminuria and urinary isoprostane concentration (7).Last, this study suggests that the vascular chronic obstructive pulmonary disease phenotype might benefit from antioxidant treatments.
US Republican attempt to repeal and replace Affordable Care Act collapses
Authors: Michael McCarthy
Journal: BMJ (2017)

The Republican effort to repeal and replace the Affordable Care Act (ACA) seems to have collapsed, after Republican leaders in the Senate acknowledged that they could not muster the votes needed to pass a bill despite holding a 52-48 majority in the chamber. Congressional Democrats immediately called on Republicans to join a bipartisan effort to improve the 2010 healthcare reform law, often called Obamacare.

On 17 July the Senate majority leader Mitch McConnell, a Republican from Kentucky, announced that the Senate would no longer try to pass the Senate bill after two conservative senators said that they would not support the legislation, joining two other Republicans …
Improved Outcomes in Men with Advanced Prostate Cancer
Authors: Christopher J. Logothetis
Journal: New England Journal of Medicine (2017)

The impressive and positive clinical trial results that are described by Fizazi et al.1 and James et al.2 in this issue of the Journal represent an important advance in androgen-signaling inhibition for metastatic prostate cancer. The LATITUDE and STAMPEDE research teams report encouraging improvements in the initial treatment of men with advanced prostate cancer. Metastatic, castration-sensitive prostate cancer is diagnosed in a small proportion of men with prostate cancer at initial presentation and is disproportionately represented in lethal prostate cancer. The findings of these two trials suggest that therapeutically relevant biologic features of this form of cancer are shared with . . .
Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: Is Smoker’s Paradox in Play?—Reply
Authors: Thomas Engstrøm, Dan Eik Høfsten, Henning Kelbaek
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
OC-017 Gi side effects of cancer chemotherapy- preliminary results of the foccus study
Authors: L Caley, V Pittordou, C Adams, A Lalji, K Mohammed, A Muls, L Wedlake, Hjn Andreyev
Journal: Gut (2017)

Introduction  Treatments for cancer can cause a multitude of debilitating gastrointestinal (GI) side effects. Patients are often told these are untreatable. Systematic investigation and management of GI symptoms improves outcomes after radiotherapy. No studies have investigated symptom management in chemotherapy. This prospective study aimed to identify the frequency and range of troublesome GI symptoms during and after cancer chemotherapy and identify treatable causes.  Method  GI oncology patients undergoing chemotherapy were eligible. Participants were assessed before chemotherapy and then monthly during and after treatment for one year using the Gastrointestinal Symptom Rating Scale questionnaire and the Bristol Stool Chart. If new troublesome GI symptoms arose, systematic GI investigations were offered following an algorithm.  Results  A total of 241 participants enrolled, 85 subsequently withdrew/died. 58% were men. Median age 63 years (range 30–88). 33% of participants had an oesophageal/gastric tumour, 27% colon, 16% rectal, 10% pancreatic, 6% hepatobiliary and 7% other GI sites. At its peak, approximately 20% of participants had moderate or severe change in taste, reduced appetite, early satiety or rectal flatulence, 8% faecal incontinence and 6% steatorrhoea. Overall, 35% reported type 6/7 stool (diarrhoea) and 9% type 1 stool (constipation). Algorithmic investigations identified one new coeliac, 28% had previously unrecognised abnormal thyroid function, 29% abnormal Vitamin B12 levels and 10% exocrine pancreatic insufficiency. 269 breath tests were offered, 224 (83%) were declined. Of the 45 conducted 36% were positive with 84% suggesting small bowel bacterial overgrowth, 9% lactose intolerance, 5% fructose and 2% sucrose malabsorption. There were 279 recommended endoscopic procedures, 249 (89%) were declined. Of the 30 endoscopies conducted, 60% were abnormal with inflammatory changes most commonly being diagnosed. SeHCAT scans (testing for bile acid malabsorption) were offered 146 times and declined 119 times. Of the 27 conducted, 13 (48%) were abnormal.  Conclusion  GI symptoms are common and troublesome during chemotherapy for cancer. Simple questionnaires can identify patients requiring investigations. The assumption that GI chemotherapy-induced symptoms are untreatable is frequently incorrect. Investigational algorithms designed for use by non-gastroenterologists are effective, but patients often refuse tests. Active management of GI symptoms may improve outcomes. Further research is urgently required. This study was funded by The Philip Gould Fund and the Biomedical Research Centre at the Royal Marsden Hospital.  Disclosure of Interest  L. Caley: None Declared, V. Pittordou: None Declared, C. Adams: None Declared, A. Lalji: None Declared, K. Mohammed: None Declared, A. Muls: None Declared, L. Wedlake: None Declared, H. J. Andreyev Conflict with: GE, manufacturers of SeHCAT provided free product for this study
Abstract #1700: Amonafide (AS1413) intercalates into DNA and is a unique inhibitor of DNA Topoisomerase II
Authors: Yoko Otake, MyDoanh Chau, Robert Capizzi, Daniel Fernandes
Journal: Cancer Research (2009)

Amonafide (AS1413, amonafide L-malate) has shown activity in phase I and II clinical trials in patients with secondary AML (sAML) and is now in a pivotal phase III clinical trial in sAML. The drug\#8217;s clinical activity prompted further investigation of its mechanism of action. Our results showed that amonafide is a potent DNA topoisomerase II (Topo II)-active drug that differs from the classical Topo II inhibitors (daunorubicin, etoposide, mitoxantrone) in its reactivity towards Topo II-DNA complexes and because it is neither a substrate nor an inhibitor of P-glycoprotein. Specifically, amonafide intercalated into DNA and both inhibited the binding of human Topo II to DNA and interfered with ATP binding to Topo II in DNA decatentation assays. Amonafide also blocked the etoposide-induced cleavage of pRYG DNA. These data indicate that amonafide inhibits Topo II catalysis prior to the formation of Topo II-DNA cleavable complexes and suggest that amonafide induces less DNA damage than the classical Topo II inhibitors. In contrast to daunorubicin and etoposide, the IC 50  concentration of amonafide induced apoptosis in MV4-11 leukemia cells without inducing significant \#947;-histone-2AX phosphorylation, which occurs after the induction of DNA double-strand breaks. Furthermore, significant cell surface expression of NG2 (neuron-glial antigen 2), a biomarker associated with MLL gene fusions, was not observed in CEM cells treated with IC 50   concentrations of amonafide. When CEM or MV4-11 cells were incubated with concentrations of amonafide, etoposide, or daunorubicin that induced similar degrees of apoptosis, amonafide treatment resulted in only high molecular weight DNA fragmentation (50-300 kb), while etoposide and daunorubicin treatment resulted in extensive cleavage of DNA into fragments less than 50 kb. These results indicate that the mechanism of action of amonafide is distinct from the classical Topo II-active drugs. Our data are consistent with a chromatin disorganization model in which amonafide triggers apoptosis via inhibition of Topo II, which induces the release of single (50 kb) and multiple chromatin loops (>50 kb) from their attachment sites on the nuclear matrix.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1700.
A Rapid Desensitization Program Is a Viable Therapeutic Option in the Management of Immunomodulating Agent-Related Hypersensitivity Reactions in Patients with Plasma Cell Disorders
Authors: Jack T Seki, Naoko Sakurai, Wallace Lam, Vesna Lukaroska, Anna Granic, Patricia Disperati, Amy Tam, Suzanne Trudel, Donna Reece
Journal: Blood (2016)