A user-friendly risk-score for predicting in-hospital cardiac arrest among patients admitted with suspected non ST-elevation acute coronary syndrome – the SAFER-score

Aim: To develop a simple risk-score model for predicting in-hospital cardiac arrest (CA) among patients hospitalized with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART), we identified patients (n = 242 303) admitted with suspected NSTE-ACS between 2008 and 2014. Logistic regression was used to assess the association between 26 candidate variables and in-hospital CA. A risk-score model was developed and validated using a temporal cohort (n = 126 073) comprising patients from SWEDEHEART between 2005 and 2007 and an external cohort (n = 276 109) comprising patients from the Myocardial Ischaemia National Audit Project (MINAP) between 2008 and 2013. Results: The incidence of in-hospital CA for NSTE-ACS and non-ACS was lower in the SWEDEHEART-derivation cohort than in MINAP (1.3% and 0.5% vs. 2.3% and 2.3%). A seven point, five variable risk score (age ≥60 years (1 point), ST-T abnormalities (2 points), Killip Class >1 (1 point), heart rate <50 or ≥100 bpm (1 point), and systolic blood pressure <100 mmHg (2 points) was developed. Model discrimination was good in the derivation cohort (c-statistic 0.72) and temporal validation cohort (c-statistic 0.74), and calibration was reasonable with a tendency towards overestimation of risk with a higher sum of score points. External validation showed moderate discrimination (c-statistic 0.65) and calibration showed a general underestimation of predicted risk. Conclusions: A simple points score containing five variables readily available on admission predicts in-hospital CA for patients with suspected NSTE-ACS

Standardized Outcome Measurement for Patients With Coronary Artery Disease: Consensus From the International Consortium for Health Outcomes Measurement (ICHOM)

Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. The International Consortium for Health Outcomes Measurement (ICHOM) established a Working Group to define a standard set of outcome measures and risk factors of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the Group defined who should be tracked, what should be measured, and when such measurements should be performed. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient‐reported health status (Seattle Angina Questionnaire [SAQ‐7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ‐2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons

A Chemical Genomics Approach to Drug Reprofiling in Oncology: Antipsychotic Drug Risperidone as a Potential Adenocarcinoma Treatment

Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag® chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-β-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-β-HSD10 identifies risperidone as a drug reprofiling candidate. When formulated with rumenic acid, risperidone slows proliferation of PC3 prostate cancer cells in vitro and retards PC3 prostate cancer tumour growth in vivo in xenografts in mice, presenting an opportunity to reprofile risperidone as a cancer treatment

Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction:-The SWEDEHEART Score

Background: Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in‐hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results: From the nationwide SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) scores. Internal and temporal validity was assessed. In‐hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C‐reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall (C‐index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions: The 5‐item SWEDEHEART score discriminates in‐hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores

Spirulina Promotes Stem Cell Genesis and Protects against LPS Induced Declines in Neural Stem Cell Proliferation

Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1β in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFα to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study

Background Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. Methods Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin – Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. Results A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73–4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69–1.33). Conclusions This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population

Flexor Hallucis Longus tendon rupture in RA-patients is associated with MTP 1 damage and pes planus

<p>Abstract</p> <p>Background</p> <p>To assess the prevalence of and relation between rupture or tenosynovitis of the Flexor Hallucis Longus (FHL) tendon and range of motion, deformities and joint damage of the forefoot in RA patients with foot complaints.</p> <p>Methods</p> <p>Thirty RA patients with painful feet were analysed, their feet were examined clinically for the presence of pes planus and range of motion (ROM), radiographs were scored looking for the presence of forefoot damage, and ultrasound examination was performed, examining the presence of tenosyovitis or rupture of the FHL at the level of the medial malleolus. The correlation between the presence or absence of the FHL and ROM, forefoot damage and pes planus was calculated.</p> <p>Results</p> <p>In 11/60(18%) of the feet, a rupture of the FHL was found. This was associated with a limited motion of the MTP1-joint, measured on the JAM (χ²= 10.4, p = 0.034), a higher prevalence of pes planus (χ²= 5.77, p = 0.016) and a higher prevalence of erosions proximal at the MTP-1 joint (χ²= 12.3, p = 0.016), and joint space narrowing of the MTP1 joint (χ²= 12.7, p = 0.013).</p> <p>Conclusion</p> <p>Rupture of the flexor hallucis longus tendon in RA-patients is associated with limited range of hallux motion, more erosions and joint space narrowing of the MTP-1-joint, as well as with pes planus.</p

Phylogeographic analysis reveals multiple international transmission events have driven the global emergence of Escherichia coli O157:H7

This work was supported by: Scotland by Food Standards Scotland [Grant Number FS102029] and University of Aberdeen; New Zealand, Institute of Environmental Science and Research; Canada, the Public Health Agency of Canada; United States, United States Department of AgriculturePeer reviewedPostprin

Targeting the IGF-1R signaling and mechanisms for epigenetic gene silencing in human multiple myeloma

Multiple myeloma (MM) is a B cell malignancy characterized by the expansion of clonal plasmablast/plasma cells within the bone-marrow. It is well established that the bone-marrow microenvironment has a pivotal role in providing critical cytokines and cell–cell interactions to support the growth and survival of the MM tumor clone. The pathogenesis of MM is, however, only fragmentarily understood. Detailed genomic analysis reveals a heterogeneous and complex pattern of structural and numerical chromosomal aberrations. In this review we will discuss some of the recent results on the functional role and potential clinical use of the IGF-1R, one of the major mediators of growth and survival for MM. We will also describe some of our results on epigenetic gene silencing in MM, as it may indeed constitute a novel basis for the understanding of tumor initiation and maintenance in MM and thus may change the current view on treatment strategies for MM

International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries

To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registrie