tbuckley/cabot-search huggingface dataset:
IMPACT OF BASELINE ANXIETY ON ARRHYTHMIA-FREE SURVIVAL AND QUALITY OF LIFE IN ATRIAL FIBRILLATION PATIENTS UNDERGOING CATHETER ABLATION
Authors: Sanghamitra Mohanty, Chintan Trivedi, Carola Gianni, Vivek Bhupathi, Domenico Giovanni Della Rocca, John Burkhardt, Rodney Horton, Gerald Gallinghouse, Javier Sanchez, Luigi Di Biase, Andrea Natale
Journal: Journal of the American College of Cardiology (2018)
Rethinking the National Diabetes Prevention Program for Low-Income Whites
Authors: Natalie D. Ritchie, Katherine A. Sauder, Phoutdavone Phimphasone-Brady, Claudia R. Amura
Journal: Diabetes Care (2018)

The National Diabetes Prevention Program (NDPP) is a widely disseminated lifestyle intervention to prevent diabetes through weight loss. Racial/ethnic disparities in NDPP effectiveness have been shown, with non-Hispanic whites (NHWs) losing more weight than Hispanics and non-Hispanic blacks (NHBs) (1). Income disparities in NDPP effectiveness are understudied, yet they are relevant for future Medicaid coverage of the program. We previously reported a lower-than-average weight loss for NHWs participating in the NDPP within a health care system for underserved populations (2). Here, we examined whether income status modifies the association between race/ethnicity and NDPP outcomes.

The NDPP was implemented in a safety-net health care system following Centers for Disease Control and Prevention (CDC) guidelines (3). Effectiveness was evaluated among 994 Hispanic, NHB, and NHW participants. The Colorado Multiple Institutional Review Board approved this program evaluation project. Race/ethnicity, income, age, sex, and BMI were collected from medical records. Income was classified …
PREVALENCE AND COMPLICATIONS OF ABERRANT RIGHT SUBCLAVIAN ARTERY IN CHINESE POPULATION
Authors: Huanyu Ding, Binquan Hu, Yuan Liu, Wenhui Huang, Songyuan Luo, Yi Zhu, Minchun Jiang, Ling Xue, Nianjin Xie, Jie Li, Jiyan Chen, Ruixin Fan, Jianfang Luo
Journal: Journal of the American College of Cardiology (2018)
P060 Il-38 in arthritis maturation and degradation of this new IL-1 family anti-inflammatory cytokine
Authors: M Harel, T Garraud, B Le Goff, F Blanchard
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Interleukin 38 (IL-38) is an IL-1 family cytokine with potential anti-inflammatory activity. Recently we showed that over-expression of full length IL-38 reduces inflammation in arthritic mice by 20%–30%, reduces macrophage infiltration and the expression of cytokines implicated in the biology of Th17 cells.<sup>1</sup> However, IL-38 does not have a classical signal peptide, and it is unclear how it is released for example from monocytes/macrophages. It needs post-translational processing (N-terminal truncation) to acquire full biological activity, but the required proteases are unknown. <h3>Objectives</h3> The aim is to study the maturation of IL-38 in the inflammatory process. <h3>Methods</h3> THP1 macrophagic cells were transduced with a lentivirus encoding full length IL-38 to over-express this cytokine. Secretion and maturation (truncation) of endogenous or over-expressed IL-38 has been studied by western blot. The potential proteases implicated in IL-38 N-terminal truncation have been analysed <i>in silico</i> (Prosper webserver) and by biochemical tests using recombinant proteases and their inhibitors. <h3>Results</h3> In the synovial fluid of RA patients, we observed 2 truncated forms of IL-38. To determine if apoptosis is a mechanism responsible for the maturation of IL-38, we tested different stress conditions on THP1 macrophages that overexpress IL-38. In conditioned media, three truncated forms of IL-38 were revealed by Western Blot under conditions of apoptosis, exacerbated oxidative stress, or necrosis. However, none of these conditioned media appears to have a high anti-inflammatory effect on macrophages. Our results rather suggest that cell death by apoptosis or necrosis results in IL-38 degradation and loss of biological effect. <i>In silico</i>, several potential cleavage sites were found for calpain, MMP-2, MMP-9 and cathepsin G. Incubation of recombinant full length IL-38 with MMP-2 or cathepsin G leads to significant degradation of this cytokine. On apoptotic THP1 cells overexpressing IL-38, an inhibitor of MMPs and TACE (TAPI) also reduces the release and degradation of IL-38. <h3>Conclusions</h3> The degradation and loss of the anti-inflammatory effect of IL-38 appears to occur during cell death in the extracellular space, and could involve MMPs. The processes involved in the maturation of IL-38 need to be further explored and could open new therapeutic opportunities for the treatment of arthritis. <h3>Reference</h3> . Boutet MA, et al. IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro. Ann Rheum Dis2017;76:1304–1312. <h3>Disclosure of interest</h3> M. Harel: None declared, T. Garraud: None declared, B. Le Goff: None declared, F. Blanchard Grant/research support from: Inserm, the Arthritis Foundation, the French Society of Rheumatology, Pfizer and the Région Pays de la Loire (Bioregate)
Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident Diabetes and Insulin Resistance in the Strong Heart Family Study
Authors: Maria Grau-Perez, Chin-Chi Kuo, Matthew O. Gribble, Poojitha Balakrishnan, Miranda Jones Spratlen, Dhananjay Vaidya, Kevin A. Francesconi, Walter Goessler, Eliseo Guallar, Ellen K. Silbergeld, Jason G. Umans, Lyle G. Best, Elisa T. Lee, Barbara V. Howard, Shelley A. Cole, Ana Navas-Acien
Journal: Environmental Health Perspectives (2017)

High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity.We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up.Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants.Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.
Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse
Authors: Zinaida Good, Jolanda Sarno, Astraea Jager, Nikolay Samusik, Nima Aghaeepour, Erin F Simonds, Leah White, Norman J Lacayo, Wendy J Fantl, Grazia Fazio, Giuseppe Gaipa, Andrea Biondi, Robert Tibshirani, Sean C Bendall, Garry P Nolan, Kara L Davis
Journal: Nature Medicine (2018)
Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock
Authors: Lucie Jolly, Kevin Carrasco, Marc Derive, Jérémie Lemarié, Amir Boufenzer, Sébastien Gibot
Journal: Cardiovascular Research (2018)

TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor expressed on neutrophils and monocytes/macrophages whose role is to amplify the inflammatory response driven by Toll-Like Receptors engagement. The pharmacological inhibition of TREM-1 confers protection in several pre-clinical models of acute inflammation. In this study, we aimed to decipher the role of TREM-1 on the endothelium.We first showed by qRT-PCR, flow cytometry and confocal microscopy that TREM-1 was expressed in human pulmonary microvascular endothelial cells as well as in mouse vasculature (aorta, mesenteric artery, and pulmonary vessels). TREM-1 expression was upregulated following septic insult. We next observed that TREM-1 engagement impaired mouse vascular reactivity and promoted vascular inflammation. The pharmacological inhibition of TREM-1 (using the synthetic inhibitory peptide LR12) prevented these disorders both in vitro and in vivo. We generated endothelium-conditional Trem-1 ko mice (EndoTREM-1-/-) and submitted them to a caecal ligation and puncture-induced septic shock. As compared with wild-type littermates, targeted endothelial Trem-1 deletion conferred protection during septic shock in modulating inflammatory cells mobilization and activation, in restoring vasoreactivity, and in improving the survival.We reported that TREM-1 is expressed and inducible in endothelial cells and plays a direct role in vascular inflammation and dysfunction. The targeted deletion of endothelial Trem-1 conferred protection during septic shock in modulating inflammatory cells mobilization and activation, restoring vasoreactivity, and improving survival. The effect of TREM-1 on vascular tone, while impressive, deserves further investigations including the design of endothelium-specific TREM-1 inhibitors.
Letter to the editor: Comment on the Regulatios of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine
Authors: Shilin Chen, Aihua Liang, Boli Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

On Oct 9, 2017, China Food and Drug Administration announced 1 the Regulations of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine (Exposure Draft) which has been stirring up intense debate in the West.The article China to Roll Back Regulations for Traditional Medicine Despite Safety Concerns lately published on Nature 2 has raised worldwide attention by stressing its worries over the safety issue of traditional Chinese herbal medicines.However, we noticed that classic Chinese herbal formulations with long-term traditional use are not yet well known to the Western world.Hereby we intend to elaborate on a clearer picture of classic Chinese herbal formulations and to offer a better understanding to the western researchers.In our study, the classic Chinese herbal formulations only refer to those quoted from the ancient Chinese medical classics prior to 1911 which have conformed with the same stringent examination, regulation model, and approval standards as other medications in China since the implementation of "Provisions for Drug Registration" in 1985.In 2016, the China Food and Drug Administration (CFDA) approved only two types of new classic Chinese formulations, yet hundreds of chemical and biological drugs.Effects of classic Chinese herbal formulations, though being proved by hundreds of years' clinical application, have to over and over again go through time-consuming and costly lab tests.It is the indiscriminate regulation that slows down the development of classic Chinese herbal formulations.In fact, the traditional herbal medicines and modern biochemical drugs differ both in pharmacology and in applications history.Therefore we suggest that the current regulation policy for chemical drugs should not be applied to Chinese herbal medicines without any adjustment.Based on this characteristic, CFDA plans to adopt a simplified registration and approval management.This is beneficial to speed up the launch of new drugs of Chinese herbal medicines, reduce the research and development cost, ease the burden of medical care, achieve WHO's accessibility and affordability on traditional drugs and promote the goal for TCM to serve human health 3 .
I am working as a senior house officer on a surgical rotation and I plan to complete my MRCS soon. I am interested in a career in radiology—what should I do in the meantime to improve my chances?
Authors: Sarah Burnett
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Drivers for treatment in an active surveillance cohort.
Authors: Philip Gilbo, Mark Hamilton, Louis Potters, Brett Wayne Cox
Journal: Journal of Clinical Oncology (2018)

66 Background: Active Surveillance (AS) for Prostate Cancer (CaP) has become an established management option for patients (pts) with low-risk CaP. We examined the drivers of selecting treatment (tx) over time from a cohort of AS pts seen in a radiation oncology department. Methods: Pts seen in consultation with low-risk CaP were offered AS as one management option. A review of 2,545 pt charts with newly diagnosed CaP from 2010-2016 was undertaken with 794 (31.2%) meeting criteria for AS and ultimately 166 (20.6%) of those patients choosing AS within our department. 22 patients opted to discontinue surveillance before their confirmatory studies. Results: 145 pts elected AS and 66 (45.5%) ultimately required or chose tx. 138 (81.3%) of patients had Gleason 3+3, 28 (17%) had Gleason 3+4 and 3 (1.8%) had Gleason 4+3. The majority (96.4%) were T1c and 112 (67%) were characterized as having NCCN very low risk with a mean PSA of 5.38ng/mL (± 2.38ng/mL). Of the 66 pts who underwent tx, 36 (54.7%) were due to an increase in Gleason score or PSA rise, 14 (21%) electively decided against further AS, 6 (9%) for radiographic progression and 10 (15%) for other. Tx choices are presented in Table 1 with 54 pts (81%) choosing a radiotherapeutic (RT) intervention. The median time to initiate tx was 3.8 years from diagnosis. Conclusions: Men with low-risk CaP and eligible for AS elected AS 21% of the time with slightly less than half of the AS cohort converting to tx within 4 years. The main drivers for tx was either an increase in Gleason score or rise in PSA, followed by patient anxiety regarding diagnosis. Trends over time identified an increase in men electing AS but additional efforts are underway to educate pts on informed decision making and addressing diagnosis anxiety to maintain AS status. A significant proportion of patients chose a RT intervention, perhaps reflecting tx bias towards the physician performing the surveillance. [Table: see text]
URIC ACID PREDICTS CORONARY ARTERY DISEASE BUT NOT STROKE IN ESSENTIAL HYPERTENSION: DATA FROM A GREEK 8-YEAR-FOLLOW-UP STUDY
Authors: Konstantinos P. Tsioufis, Kyriakos Dimitriadis, Alexandros Kasiakogias, Dimitrios Konstantinidis, Spyros Galanakos, Theodoros Kalos, Ioanna Karapati, Eirini Andrikou, Manos Mantzouranis, Christos Fragoulis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
FEWER DEATHS OR HOSPITALIZATIONS FOR HEART FAILURE USING HYDRALAZINE-ISOSORBIDE MONONITRATE COMPARED TO HYDRALAZINE-ISOSORBIDE DINITRATE IN PATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Bradley Peltzer, Tonusri Nag, Yekaterina Kim, Allen Weiss, Salil Kumar, Eric Shulman, J. Julia Shin, Snehal Patel, Omar Saeed, Ulrich Jorde, Daniel Sims
Journal: Journal of the American College of Cardiology (2018)
Long-term Outcomes Associated With Implantable Cardioverter Defibrillator in Adults With Chronic Kidney Disease
Authors: Nisha Bansal, Adam Szpiro, Kristi Reynolds, David H. Smith, David J. Magid, Jerry H. Gurwitz, Frederick Masoudi, Robert T. Greenlee, Grace H. Tabada, Sue Hee Sung, Ashveena Dighe, Alan S. Go
Journal: JAMA Internal Medicine (2018)

Chronic kidney disease (CKD) is common in adults with heart failure and is associated with an increased risk of sudden cardiac death. Randomized trials of participants without CKD have demonstrated that implantable cardioverter defibrillators (ICDs) decrease the risk of arrhythmic death in selected patients with reduced left ventricular ejection fraction (LVEF) heart failure. However, whether ICDs improve clinical outcomes in patients with CKD is not well elucidated.To examine the association of primary prevention ICDs with risk of death and hospitalization in a community-based population of potentially ICD-eligible patients who had heart failure with reduced LVEF and CKD.This noninterventional cohort study included adults with heart failure and an LVEF of 40% or less and measures of serum creatinine levels available from January 1, 2005, through December 31, 2012, who were enrolled in 4 Kaiser Permanente health care delivery systems. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2. Patients who received and did not receive an ICD were matched (1:3) on CKD status, age, and high-dimensional propensity score to receive an ICD. Follow-up was completed on December 31, 2013. Data were analyzed from 2015 to 2017.Placement of an ICD.All-cause death, hospitalizations due to heart failure, and any-cause hospitalizations.A total of 5877 matched eligible adults with CKD (1556 with an ICD and 4321 without an ICD) were identified (4049 men [68.9%] and 1828 women [31.1%]; mean [SD] age, 72.9 [8.2] years). In models adjusted for demographics, comorbidity, and cardiovascular medication use, no difference was found in all-cause mortality between patients with CKD in the ICD vs non-ICD groups (adjusted hazard ratio, 0.96; 95% CI, 0.87-1.06). However, ICD placement was associated with increased risk of subsequent hospitalization due to heart failure (adjusted relative risk, 1.49; 95% CI, 1.33-1.60) and any-cause hospitalization (adjusted relative risk, 1.25; 95% CI, 1.20-1.30) among patients with CKD.In a large, contemporary, noninterventional study of community-based patients with heart failure and CKD, ICD placement was not significantly associated with improved survival but was associated with increased risk for subsequent hospitalization due to heart failure and all-cause hospitalization. The potential risks and benefits of ICDs should be carefully considered in patients with heart failure and CKD.
The clinical analysis of thromboembolism in esophagogastric cancer in Japan: A single institute experience.
Authors: Tomoyo Oguri, Daisuke Takahari, Yumiko Ota, Hiroki Osumi, Izuma Nakayama, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Mitsukuni Suenaga, Eiji Shinozaki, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2018)

14 Background: Although patients with esophagogastric cancer have a higher risk of thromboembolism (TE), the clinical characteristics of esophagogastric cancer patients with TE remain unclear. Methods: We conducted a retrospective study of who were treated for TE in our institution from January 2014 to August 2017. Results: During this period, 1538 esophaogastic cancer patients received anti cancer therapy. Of these 62 (4.0%) patients diagnosed as having TE during their clinical course. Background of these patitents were median age :64.5 (28-87), gender male/ female: 36 /26, 47 had gastric cancer, 12 esophageal cancer, and 2 gastroesophageal cancer. Performance Status were 0/1/2/3 = 21/24/13/4. Clinical stage were Ⅳ 32 (metastatic sites; lymph nodes 7, peritoneal dissemination 6, ovary 4, liver 1), recurrence 18, and other 12 respectively. 26 patients did not have medical history, 15 had hypertension, 4 had diabetes mellitus, and 4 had hyperlipidemia. Pathologically, adenocarcinoma 50, squamous carcinoma 10, and other 2. Among patients with gastric cancer, 6 (12.8%) showed Her2 overexpression. The median D-dimer levels was 4.81(0.42-17.25) μg/ml. The onset of TE was before starting chemotherapy in 8(12.9%), during receiving chemotherapy in 48(77.4%), and during washout period in 6. On patients who developed TE during receiving chemotherapy, the regimens of chemotherapy were S-1 16, weekly paclitaxel 10 (plus ramucirumab 3), SOX 7, FP 4, Irinotecan 3, SP 3, FOLFOX 3, XP+Trastuzumab3, and others 9. The types of venous thrombosis were deep vein thrombosis 33, pulmonary embolism 23, central venous catheter 7, internal jugular vein 5, subclavian vein 4, and others 5. Four patients suffered cerebral infarction due to thrombosis of the arterial system thrombosis. Initial anticoagulation treatment for TE were heparin 33, warfarin 13, edoxaban 12 and other 4. 29 patients (46.8%) had no symptom related TE. Conclusions: In our analysis, 12.9% patients had TE before starting treatment, we should pay attention to TE immediately after diagnosis of esophagogastric cancer. As 46.8% patients have no symptom related TE, it is important to develop of biomarkers for screening TE, likely D-dimer.
Can I do an MSc in respiratory medicine while doing a senior house officer job?
Authors: Andrew Whitehouse
Journal: BMJ (2004)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.