Showing papers by "Beaumont Health published in 2016"

Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE.

Abstract: AMI : acute myocardial infarction ARVC : arrhythmogenic right ventricular cardiomyopathy BrS : Brugada syndrome CACS : coronary artery calcium score CAD : coronary artery disease ChD : Chagas heart disease CMR : cardiac magnetic resonance CPVT : catecholaminergic polymorphic ventricular tachycardia CTCA : computed tomography coronary angiography CV : cardiovascular DCM : dilated cardiomyopathy EAPCR : European Association for Cardiovascular Prevention and Rehabilitation HCM : hypertrophic cardiomyopathy LGE : late gadolinium enhancement LQTS : long QT syndrome LV/RV : left/right ventricle LVH : left ventricle hypertrophy NSVT : non-sustained ventricular tachycardia PPE : preparticipation evaluation PVC : premature ventricular contractions SCA/SCD : sudden cardiac arrest/death TTE : transthoracic echocardiography VF : ventricular fibrillation VT : ventricular tachycardia Sudden cardiac death (SCD) associated with athletic activity is a rare but devastating event. Victims are usually young and apparently healthy, and while many of these deaths remain unexplained, a substantial number of victims harbour an underlying and potentially detectable cardiovascular (CV) disease.1–4 The vast majority of these events are due to malignant tachyarrhythmias, usually ventricular fibrillation (VF) or ventricular tachycardia (VT) degenerating into ventricular fibrillation (VF), occurring in individuals with arrhythmogenic disorders (e.g. hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, channelopathies). Intensive exercise training and competitive sport participation is a trigger that may favour insurgence of ominous ventricular tachyarrhythmias in predisposed individuals.5 Consequently, there is a great interest in early identification of at-risk individuals for whom appropriate treatment, followed or not by physical activity adjustment, may be implemented to minimize the risk of SCD. However, the role of pre-participation evaluation (PPE) in athletes as a feasible and efficient strategy to identify individuals at risk has remained controversial. …

The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer

Abstract: CD44 is a cell surface HA-binding glycoprotein that is overexpressed to some extent by almost all tumors of epithelial origin and plays an important role in tumor initiation and metastasis. CD44 is a compelling marker for cancer stem cells of many solid malignancies. In addition, interaction of HA and CD44 promotes EGFR-mediated pathways, consequently leading to tumor cell growth, tumor cell migration, and chemotherapy resistance in solid cancers. Accumulating evidence indicates that major HA-CD44 signaling pathways involve a specific variant of CD44 isoforms; however, the particular variant almost certainly depends on the type of tumor cell and the stage of the cancer progression. Research to date suggests use of monoclonal antibodies against different CD44 variant isoforms and targeted inhibition of HA/CD44-mediated signaling combined with conventional radio/chemotherapy may be the most favorable therapeutic strategy for future treatments of advanced stage malignancies. Thus, this paper briefly focuses on the association of the major CD44 variant isoforms in cancer progression, the role of HA-CD44 interaction in oncogenic pathways, and strategies to target CD44-overexpressed tumor cells.

Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation.

Abstract: Background:Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated...

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism

Abstract: Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Clinical and Radiographic Outcomes of the Simpliciti Canal-sparing Shoulder Arthroplasty System: A Prospective Two-year Multicenter Study

Abstract: Background: Stemmed humeral components have been used since the 1950s; canal-sparing (also known as stemless) humeral components became commercially available in Europe in 2004. The Simpliciti total shoulder system (Wright Medical, formerly Tornier) is a press-fit, porous-coated, canal-sparing humeral implant that relies on metaphyseal fixation only. This prospective, single-arm, multicenter study was performed to evaluate the two-year clinical and radiographic results of the Simpliciti prosthesis in the U.S. Methods: One hundred and fifty-seven patients with glenohumeral arthritis were enrolled at fourteen U.S. sites between July 2011 and November 2012 in a U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE)-approved protocol. Their range of motion, strength, pain level, Constant score, Simple Shoulder Test (SST) score, and American Shoulder and Elbow Surgeons (ASES) score were compared between the preoperative and two-year postoperative evaluations. Statistical analyses were performed with the Student t test with 95% confidence intervals. Radiographic evaluation was performed at two weeks and one and two years postoperatively. Results: One hundred and forty-nine of the 157 patients were followed for a minimum of two years. The mean age and sex-adjusted Constant, SST, and ASES scores improved from 56% preoperatively to 104% at two years (p < 0.0001), from 4 points preoperatively to 11 points at two years (p < 0.0001), and from 38 points preoperatively to 92 points at two years (p < 0.0001), respectively. The mean forward elevation improved from 103° ± 27° to 147° ± 24° (p < 0.0001) and the mean external rotation, from 31° ± 20° to 56° ± 15° (p < 0.0001). The mean strength in elevation, as recorded with a dynamometer, improved from 12.5 to 15.7 lb (5.7 to 7.1 kg) (p < 0.0001), and the mean pain level, as measured with a visual analog scale, decreased from 5.9 to 0.5 (p < 0.0001). There were three postoperative complications that resulted in revision surgery: infection, glenoid component loosening, and failure of a subscapularis repair. There was no evidence of migration, subsidence, osteolysis, or loosening of the humeral components or surviving glenoid components. Conclusions: The study demonstrated good results at a minimum of two years following use of the Simpliciti canal-sparing humeral component. Clinical results including the range of motion and the Constant, SST, and ASES scores improved significantly, and radiographic analysis showed no signs of loosening, osteolysis, or subsidence of the humeral components or surviving glenoid components. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity.

Abstract: Purpose To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

Abstract: Purpose To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arcmulti-field) and the standard robust optimized intensity modulated proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arcmulti-field plans. Conclusion The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.

Primary Study Endpoint Analysis for NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer (NSCLC)

Abstract: NRG Oncology/RTOG 0937: Randomized Phase 2 Study Comparing Prophylactic Cranial Irradiation (PCI) Alone to PCI and Consolidative Extracranial Irradiation for Extensive Disease Small Cell Lung Cancer (ED-SCLC) E.M. Gore, C. Hu, A. Sun, D. Grimm, S. Ramalingam, N.E. Dunlap, K.A. Higgins, M. Werner-Wasik, A.M. Allen, P. Iyengar, G.M. Videtic, R.K. Hales, R.C. McGarry, J.J. Urbanic, A.T. Pu, C. Johnstone, J.N. Atkins, and J.D. Bradley; Medical College of Wisconsin, Milwaukee, WI, NRG Oncology, Philadelphia, PA, Princess Margaret Hospital, Toronto, ON, Canada, Emory University, Atlanta, GA, United States, University of Louisville, Louisville, KY, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, Rabin Medical Center, Petah Tikva, Israel, University of Texas Southwestern Medical Center, DALLAS, TX, Cleveland Clinic, Cleveland, OH, Johns Hopkins University, Baltimore, MD, United States, University of Kentucky, Lexington, KY, University of California, San Diego, La Jolla, CA, Sutter Medical Group Radiological Associates of Sacramento, Sacramento, CA, Southeast Cancer Consortium-Upstate NCORP, Goldsboro, NC, Washington University School of Medicine, St. Louis, MO

A randomized controlled trial assessing the use of ultrasound for nurse-performed IV placement in difficult access ED patients.

Abstract: Objective This study analyzed outcomes associated with nurse-performed ultrasound (US)-guided intravenous (IV) placement compared to standard of care (SOC) palpation IV technique on poor vascular access patients. Methods This was a randomized, prospective single-site study. Phase 1 involved education/training of a cohort of nurses to perform US-guided IVs. This consisted of a didactic module and hands-on requirement of 10 proctored functional IVs on live subjects. Phase 2 involved patient enrollment. emergency department patients meeting strict criteria of poor access were randomized to US-guided or SOC palpation arm. A functional IV placed by a study nurse was considered successful. Unsuccessful placement implied the study nurse failed, and a rescue IV was attempted. Time to IV placement was the total time required to obtain a functional IV and, if needed, a rescue IV. Results A total of 124 subjects were enrolled; 63 were randomized to the US-guided arm, and 61 were randomized into the SOC arm; 2 patients were excluded, leaving 59 patients. Success rate was 76% for the US-guided arm and 56% for the SOC arm (P=.02). Compared to the SOC arm, the odds ratio for success for the US-guided arm was 2.52 (95% confidence interval, 1.09-5.92). The mean time to IV placement for the US-guided arm was 15.8 and 20.7 minutes for the SOC arm (P=.75). Conclusion In difficult access patients, nurses were more successful in obtaining IV access using US guidance than palpation SOC technique. Lengthier placement times were observed more frequently when the SOC IV technique was used.

Re-irradiation stereotactic body radiotherapy for spinal metastases: a multi-institutional outcome analysis.

Abstract: OBJECTIVE This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date. METHODS The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/β of 10 for tumor and 2 for both spinal cord and cauda equina. RESULTS The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%. CONCLUSIONS Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.

BET protein inhibitor JQ1 inhibits growth and modulates WNT signaling in mesenchymal stem cells

Abstract: Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. The thienodiazepine class of BET inhibitors, such as JQ1, has been extensively studied for the potential treatment of hematological malignancies and several small molecules belonging to this class are currently under clinical investigation. While these compounds are well known to inhibit cancer cell growth and cause apoptosis, their effects on stem cells, particularly mesenchymal stem cells (MSCs), which are important for regeneration of damaged cells and tissues, are unknown. In this study we employed umbilical cord derived MSCs as a model system to evaluate the safety of JQ1. Cord derived MSCs were treated with various doses of JQ1 and subjected to cell metabolic activity, apoptosis, and cell cycle analyses using MTT assay, Annexin-V/FITC and PI staining, and flow cytometry, respectively. The effect of JQ1 on gene expression was determined using microarray and quantitative real-time reverse transcriptase polymerase chain reaction analysis. Furthermore, protein expression of apoptotic and neuronal markers was carried out using western blot and immunostaining, respectively. Our results showed that JQ1 inhibited cell growth and caused cell cycle arrest in G1 phase but did not induce apoptosis or senescence. JQ1 also down-regulated genes involved in self-renewal, cell cycle, DNA replication, and mitosis, which may have negative implications on the regenerative potential of MSCs. In addition, JQ1 interfered with signaling pathways by down regulating the expression of WNT, resulting in limiting the self-renewal. These results suggest that anticancer agents belonging to the thienodiazepine class of BET inhibitors should be carefully evaluated before their use in cancer therapy. This study revealed for the first time that JQ1 adversely affected MSCs, which are important for repair and regeneration. JQ1 specifically modulated signal transduction and inhibited growth as well as self-renewal. These findings suggest that perinatal MSCs could be used to supplement animal models for investigating the safety of anticancer agents and other drugs.

MR image-based synthetic CT for IMRT prostate treatment planning and CBCT image-guided localization.

Abstract: The purpose of this study was to propose and evaluate a method of creating a synthetic CT (S-CT) from MRI simulation for dose calculation and daily CBCT localization. A pair of MR and CT images was obtained in the same day from each of 10 prostate patients. The pair of MR and CT images was preregistered using the deformable image registration (DIR). Using the corresponding displacement vector field (atlas-DVF), the CT image was deformed to the MR image to create an atlas MR-CT pair. Regions of interest (ROI) on the atlas MR-CT pair were delineated and used to create atlas-ROI masks. 'Leave-one-out' test (one pair of MR and CT was used as subject-MR and subject-CT for evaluation, and the remaining 9 pairs were in the atlas library) was performed. For a subject-MR, autosegmentation and DVFs were generated using DIR between the subject-MR and the 9 atlas-MRs. An S-CT was then generated using the corresponding 9 paired atlas-CTs, the 9 atlas-DVFs and the corresponding atlas-ROI masks. The total 10 S-CTs were evaluated using the Hounsfield unit (HU), the calculated dose distribution, and the auto bony registration to daily CBCT images with respect to the 10 subject-CTs. HU differences (mean ± STD) were (2.4 ± 25.23), (1.18 ± 39.49), (32.46 ± 81.9), (0.23 ± 40.13), and (3.74 ± 144.76) for prostate, bladder, rectal wall, soft tissue outside all ROIs, and bone, respectively. The discrepancy of dose-volume param-eters calculated using the S-CT for treatment planning was small (≤ 0.22% with 95% confidence). Gamma pass rate (2% & 2 mm) was higher than 99.86% inside PTV and 98.45% inside normal structures. Using the 10 S-CTs as the reference CT for daily CBCT localization achieved the similar results compared to using the subject-CT. The translational vector differences were within 1.08 mm (0.37 ± 0.23 mm), and the rotational differences were within 1.1° in all three directions. S-CT created from a simulation MR image using the proposed approach with the preconstructed atlas library can replace the planning CT for dose calculation and daily CBCT image guidance.

Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy.

Abstract: Purpose The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups ( P Conclusion Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.

Intraoperative MRI for deep brain stimulation lead placement in Parkinson’s disease: 1 year motor and neuropsychological outcomes

Abstract: Traditional deep brain stimulation requires intraoperative neurophysiological confirmation of electrode placement. Recently, purely image guided methods are being evaluated as to their clinical efficacy in comparison to surgery using microelectrode recordings. We used the ClearPoint(®) system to place electrodes in both the subthalamic nucleus and globus pallidus internus in patients with advanced Parkinson's disease. Off medication UPDRS scores were assessed before and 1 year after surgery as well as pre- and 1 year post-operative neuropsychological outcomes. Targeting precision was also assessed. Patients implanted in the subthalamic nucleus improved by 46.2 % in their UPDRS scores post-operatively (p = 0.03) whereas the globus pallidus group improved by 41 % (p = 0.06). There were no significant adverse neuropsychological outcomes in either group of patients. Mean radial error for the STN group was 1.2 ± 0.7 mm and for the GPi group 0.8 mm ± 0.3 mm. Image guided DBS using the ClearPoint(®)system has high targeting precision with robust clinical outcomes. Our data are in accord with recent studies using the same or similar technologies and provide a rationale for a large comparative study of image-guided versus microelectrode guided DBS.

Cancer Immunology and Immunotherapy

Abstract: Hanahan and Weinberg described six distinct biological properties of cancer cells that enable tumor growth and metastasis These properties were referred to as the traditional hallmarks of cancer Recent discoveries further elucidated hallmarks including evasion of immune destruction by tumor cells that disrupt anticancer response pathways This review discusses cancer immunology and new treatment strategies aimed at restoration of antitumor immune responses

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer

Abstract: Treatment of intermediate and high-risk prostate cancer with a high BED has been shown to increase recurrence free survival (RFS). While high dose rate (HDR) brachytherapy, given as a boost is effective in delivering a high BED, many patients are not candidates for the procedure or wish to avoid an invasive procedure. We evaluated the use of stereotactic body radiotherapy (SBRT) as a boost, with dosimetry modeled after HDR-boost. Fifty patients were treated with two fractions of SBRT (9.5-10.5 Gy/fraction) after 45 Gy external-beam radiotherapy, with 48 eligible for analysis at a median follow-up of 42.7 months. The Kaplan-Meier estimates of biochemical control post-radiation therapy (95 % Confidence Interval) at 3, 4 and 5 years were 95 % (81–99 %), 90 % (72–97 %) and 90 % (72–97 %), respectively (not counting 2 patients with a PSA bounce as failures). RFS (defined as disease recurrence or death) estimates at 3, 4 and 5 years were 92 % (77–97 %), 88 % (69–95 %) and 83 % (62–93 %) if patients with PSA bounces are not counted as failures, and were 90 % (75–96 %), 85 % (67–94 %) and 75 % (53–88 %) if they were. The median time to PSA nadir was 26.2 months (range 5.8–82.9 months), with a median PSA nadir of 0.05 ng/mL (range <0.01–1.99 ng/mL). 2 patients had a “benign PSA bounce”, and 4 patients recurred with radiographic evidence of recurrence beyond the RT fields. Treatment was well tolerated with no acute G3 or higher GI or GU toxicity and only a single G3 late GU toxicity of urinary obstruction. SBRT boost is well-tolerated for intermediate and high-risk prostate cancer patients with good biochemical outcomes and low toxicity.

Comparison of Demographics, Tumor Characteristics, and Survival Between Pancreatic Adenocarcinomas and Pancreatic Neuroendocrine Tumors: A Population-based Study.

Abstract: The objective of this study is to compare the incidence, demographics, tumor characteristics, and survival between patients with pancreatic neuroendocrine tumors (PNETs) and pancreatic adenocarcinomas. Between 2004 and 2012, all cases of pancreatic adenocarcinomas and PNETs were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program. To identify the cases, a combination of topographical and histology codes based on ICD-O-3 were used. Incidence, demographics, tumor characteristics, and survival was then compared between these 2 histologic subtypes of pancreatic cancer. A total of 57,688 patients with pancreatic cancer were identified, of which 53,753 (93%) had pancreatic adenocarcinoma and 3935 (7%) had PNET. The overall age-adjusted incidence of PNETs between 2004 and 2012 was 0.52 per 100,000 per year, whereas that for pancreatic adenocarcinomas during the same period was 7.34 per 100,000 per year. PNETs had a significantly younger median age at diagnosis (61 vs. 69 y). A significant proportion of PNETs were diagnosed at stage I (20.5% vs. 6.0%) and were well differentiated (32.8% vs. 4.5%) compared with adenocarcinomas. Five-year cause-specific survival was 51.3% and 5.0% for PNETs and pancreatic adenocarcinomas, respectively. In multivariate analysis, pancreatic adenocarcinomas had a hazard ratio for death of 4.02 (95% confidence interval, 3.79-4.28) when compared with PNETs. PNETs present with favorable features such as higher proportion of early-stage tumor, higher proportion of well differentiated tumors, and younger age at diagnosis. PNETs have a significantly better survival than pancreatic adenocarcinomas even after adjusting for age, sex, race, site, grade, and stage.

Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS.

Abstract: Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia.

High resolution metabolomic analysis of ASD human brain uncovers novel biomarkers of disease

Abstract: Autism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no reliable clinical biomarkers are available for early detection. This study aimed to biochemically profile the cerebellum from post-mortem human brain from ASD sufferers (n = 11) and compare their profiles to that of age-matched controls (n = 11) with no known brain disorder. Using liquid chromatography combined with LTQ-Orbitrap mass spectrometry we detected 14,328 features in ESI+ mode in polar extracts of post-mortem brain. Of these only 37 were found to be statistically significantly different between ASD and controls (p < 0.05; fdr < 0.05). A panel of four features had a predictive power of 96.64 %, following statistical cross validation, for ASD detection. This model produced an AUC = 0.874 (CI 0.768–0.944) and a Fisher’s exact score of p = 4.50E−29. Whilst at this time we were unable to chemically identify the four features of interest we believe that this study underscores the potential value of high resolution metabolomics for the study of ASD. Further characterization of the polar metabolome of post mortem ASD brains could lead to the identification of potential biomarkers and novel therapeutics for the disease. The development of accurate biomarkers could assist in the early detection of ASD and promote early intervention strategies to improve outcome.

Physical Therapists' Role in Health Promotion as Perceived by the Patient: Descriptive Survey

Abstract: Background The importance of health professionals discussing health behaviors with patients is emphasized in Healthy People 2020, the national health objectives established by the US Department of Health and Human Services. Many physical therapists do not routinely discuss health behaviors with their patients. One reason may be uncertainty about how these discussions might be perceived by patients. Objective The primary purpose of this study was to determine patients' opinions regarding physical therapists discussing the topics of physical activity, smoking, fruit and vegetable consumption, and maintaining a healthy weight during clinical visits. A secondary purpose was to determine whether patients believe that physical therapists should be role models for these behaviors. Design This was a descriptive cross-sectional survey. Methods Patients were surveyed at 8 outpatient clinics in Michigan and Minnesota. A written questionnaire collected information about the participants' health behaviors, their opinions about physical therapists discussing their health behaviors during clinical visits, and their opinions about physical therapists role-modeling healthy behaviors. Results The survey response rate was 45.6%. A total of 230 patients participated. Most participants agreed that physical therapists should speak to them about physical activity (91.3%), maintaining a healthy weight (73%), and abstaining from smoking (51.3%). Fewer participants agreed that physical therapists should advise them about fruit and vegetable consumption (32.1%). The majority of participants agreed that physical therapists should be role models for engaging in regular physical activity (83.4%), maintaining a healthy weight (71.7%), and abstaining from smoking (63.9%). Limitations Limitations of this study include the potential for response bias and limited generalizability. Conclusions Most participants believed it is appropriate for physical therapists to speak with them about and be role models for the behaviors of physical activity, maintaining a healthy weight, and abstaining from smoking. Physical therapists have the opportunity to support the goals of Healthy People 2020 by discussing health behaviors with their patients.

SCAI/SVM expert consensus statement on carotid stenting: Training and credentialing for carotid stenting.

Abstract: Carotid artery stenting (CAS) has become an integral part of the therapeutic armamentarium offered by cardiovascular medicine programs for the prevention of stroke. The purpose of this expert consensus statement is to provide physician training and credentialing guidance to facilitate the safe and effective incorporation of CAS into clinical practice within these programs. Since publication of the 2005 Clinical Competence Statement on Carotid Stenting, there has been substantial device innovation, publication of numerous clinical trials and observational studies, accumulation of extensive real-world clinical experience and widespread participation in robust national quality improvement initiatives [5]. Collectively, these advances have led to substantial evolution in the selection of appropriate patients, as well as in the cognitive, technical and clinical skills required to perform safe and effective CAS. Herein, we summarize published guidelines, describe training pathways, outline elements of competency, offer strategies for tracking outcomes, specify facility, equipment and personnel requirements, and propose criteria for maintenance of CAS competency.