Citations

Abstract Objective Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED , saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol ( ADP ) that could safely increase the proportion of patients suitable for early discharge. Methods Logistic regression identified statistical predictors for major adverse cardiac events in a derivation cohort. Statistical coefficients were converted to whole numbers to create a score. Clinician feedback was used to improve the clinical plausibility and the usability of the final score (Emergency Department Assessment of Chest pain Score [ EDACS ]). EDACS was combined with electrocardiogram results and troponin results at 0 and 2 h to develop an ADP ( EDACS‐ADP ). The score and EDACS‐ADP were validated and tested for reproducibility in separate cohorts of patients. Results In the derivation ( n = 1974) and validation ( n = 608) cohorts, the EDACS‐ADP classified 42.2% (sensitivity 99.0%, specificity 49.9%) and 51.3% (sensitivity 100.0%, specificity 59.0%) as low risk of major adverse cardiac events, respectively. The intra‐class correlation coefficient for categorisation of patients as low risk was 0.87. Conclusion The EDACS‐ADP identified approximately half of the patients presenting to the ED with possible cardiac chest pain as having low risk of short‐term major adverse cardiac events, with high sensitivity. This is a significant improvement on similar, previously reported protocols. The EDACS‐ADP is reproducible and has the potential to make considerable cost reductions to health systems.

Significance Cancer cells reprogram their metabolism for optimal growth and survival. AMPK-activated protein kinase (AMPK) is a key energy sensor that controls many metabolic pathways including metabolic reprogramming. However, its role in cancer is poorly understood. Some studies claim that it has a tumor suppressor role while others show its protumor role. Two AMPK-activating compounds (including metformin, now in many clinical trials) are widely used to suppress cancer cell proliferation. We found that AMPK is abundantly expressed in high-grade gliomas and, in contrast to popular belief, these two AMPK activators suppressed glioma cell proliferation through unique AMPK-independent mechanisms.

Objective: The objective is to report a contemporary population-based estimate of hypoglycemia requiring emergency medical services (EMS), its burden on medical resources, and its associated mortality in patients with or without diabetes mellitus (DM, non-DM), which will enable development of prospective strategies that will capture hypoglycemia promptly and provide an integrated approach for prevention of such episodes. Methods: We retrieved all ambulance calls activated for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2009. Results: A total of 1473 calls were made by 914 people (DM 8%, non-DM 16%, unknown DM status 3%). Mean age was 60 ± 16 years with 49% being female. A higher percentage of calls were made by DM patients (87%) with proportionally fewer calls coming from non-DM patients (11%) (chi-square test, p < .001), and the remaining 2% calls by people with unknown DM status. Emergency room transportation and hospitalization were significantly higher in non-DM patients compared to DM patients ( p < .001) and type 2 diabetes mellitus compared to type 1 diabetes mellitus ( p < .001). Sulphonylureas alone or in combination with insulin varied during the study period ( p = .01). The change in incidence of EMS for hypoglycemia was tracked during this period. However, causality has not been established. Death occurred in 240 people, 1.2 (interquartile range 0.2–2.7) years after their first event. After adjusting for age, mortality was higher in non-DM patients compared with DM patients ( p < .001) but was not different between the two types of DM. Conclusions: The population burden of EMS requiring hypoglycemia is high in both DM and non-DM patients, and imposes significant burden on medical resources. It is associated with long-term mortality.

AbstractBackgroundRecent data suggest that acute coronary syndromes (ACS) and acute myocardial infarction (AMI) are characterized by an inflammatory subset of thrombosis. We have previously described the accumulation of neutrophils at the coronary culprit lesion site. In this work, we assessed the prognostic value of culprit site (CS) neutrophil accumulation on long‐term mortality in patients with AMI.Materials and methodsIn this prospective study, 417 AMI patients were enrolled after thrombectomy during primary percutaneous coronary intervention. The optimal cut‐off for CS neutrophil accumulation for predicting 4‐year all‐cause mortality was calculated using time‐dependent receiver operator characteristic curve analyses.ResultsThe median follow‐up time was 39 months interquartile range (IQR 21·4–54·6 months) corresponding to 1217 patient years of follow‐up. The cut‐off for CS neutrophil accumulation (difference between culprit neutrophil counts and systemic neutrophil counts) was 0·25 Giga/l. CS neutrophil accumulation occurred in 195 patients (47%) and was independently associated with mortality (hazard ratio 1·88 (95%CI 1·02–3·41, P = 0·043)). In patients with CS neutrophil accumulation, 1‐year mortality (10·8% vs. 7·2%) and 4‐year mortality (19·8% vs. 10·4%) were markedly increased compared with patients without local neutrophil accumulation. Concordance index for CS neutrophil accumulation and mortality was 0·64 (95% CI 0·51–0·77; P = 0·035). Patients with CS neutrophil accumulation had significantly more often nonobstructive lesions compared with patients without neutrophil accumulation (32·6% vs. 22·4%; P = 0·024).Conclusions Neutrophil accumulation at the coronary culprit lesion site is a strong and independent predictor of mortality in patients with ACS/AMI.

Background and Purpose— Several accepted algorithms exist to characterize the risk of thromboembolism in atrial fibrillation. We performed a comparative analysis to assess the predictive value of 9 such schemes. Methods— In a longitudinal community-based cohort study from Olmsted County, Minnesota, 2720 residents with atrial fibrillation were followed up for 4.4±3.6 years±SD from 1990 to 2004. Risk factors were identified using a diagnostic index integrated with the electronic medical record. Thromboembolism and cardiovascular event data were collected and analyzed. Results— We identified 350 validated thromboembolic events in our cohort. Multivariable analysis identified age >75 years (odds ratio, 2.08; P <0.0001), female sex (odds ratio, 1.45; P =0.0015), history of hypertension (odds ratio, 3.07; P <0.0001), diabetes mellitus (odds ratio, 1.58; P =0.0003), and history of heart failure (odds ratio, 1.50; P =0.0102) as significant predictors of clinical thromboembolism. The Stroke Prevention in Atrial Fibrillation (SPAF; hazard ratio, 2.75; c =0.659), CHADS 2 -revised (hazard ratio, 3.48; c =0.654), and CHADS 2 -classical (hazard ratio, 2.90; c =0.653) risk schemes were most accurate in risk stratification. The low-risk cohort within the CHA 2 DS 2 -VASc scheme had the lowest event rate among all low-risk cohorts (0.11 per 100 person-years). Conclusions— A direct comparison of 9 risk schemes reveals no profound differences in risk stratification accuracy for high-risk patients. Accurate prediction of low-risk patients is perhaps more valuable in determining those unlikely to benefit from oral anticoagulation therapy. Among our cohort, CHA 2 DS 2 -VASc performed best in this purpose.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing—of expertise and/or funding—has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

Objective: We investigated ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif, member 13) messenger RNA levels as a biomarker of disease features in systemic lupus erythematosus. Methods: We measured and compared messenger RNA (mRNA) levels of ADAMTS13 in peripheral blood cells in patients with systemic lupus erythematosus and healthy control subjects by whole-genome microarray. We retrospectively analyzed the correlations of ADAMTS13 mRNA expression with clinical features, laboratory parameters, therapeutic features, and disease activity (according to the Systemic Lupus Erythematosus Disease Activity Index). We also examined the association of three single nucleotide polymorphisms (rs4962145, rs2285467, and rs685523) of the ADAMTS13 gene with patient characteristics. Results: In 309 patients, the median ADAMTS13 mRNA expression levels were significantly higher in blood cells of systemic lupus erythematosus patients than in 23 healthy controls ( p = .03). Notably, ADAMTS13 mRNA expression levels were significantly higher in systemic lupus erythematosus patients with a history of stroke ( p = .02) or transient ischemic attack ( p = .02). Among the three single nucleotide polymorphisms analyzed, rs2285467 was significantly associated with stroke ( p = .03) and anticardiolipin antibodies ( p = .04). Conclusions: Increased expression of ADAMTS13 mRNA in blood cells is associated with the presence of ischemic cerebrovascular disease in systemic lupus erythematosus patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in these patients.