Salhia B.,Translational Genomics Research Institute |
Toms S.A.,00 North Academy Ave
International Journal of Molecular Sciences | Year: 2014
Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancer. As the length of survival in patients with systemic cancer improves, thanks to multimodality therapies, focusing on metastases to the CNS becomes of paramount importance. Unique interactions between the brain's micro-environment, blood-brain barrier, and tumor cells are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. This review will focus on the pathophysiology, epigenetics, and immunobiology of brain metastases in order to understand the metastatic cascade. Cancer cells escape the primary tumor, intravasate into blood vessels, survive the hematogenous dissemination to the CNS, arrest in brain capillaries, extravasate, proliferate, and develop angiogenic abilities to establish metastases. Molecular biology, genetics, and epigenetics are rapidly expanding, enabling us to advance our knowledge of the underlying mechanisms involved. Research approaches using cell lines that preferentially metastasize in vivo to the brain and in vitro tissue-based studies unfold new molecular leads into the disease. It is important to identify and understand the molecular pathways of the metastatic cascade in order to target the investigation and development of more effective therapies and research directions. © 2014 by the authors; licensee MDPI, Basel, Switzerland.
Dries D.,HealthPartners Medical Group |
Dries D.,University of Minnesota |
Reed M.J.,00 North Academy Ave |
Kissoon N.,University of British Columbia |
And 5 more authors.
Chest | Year: 2014
BACKGROUND: Past disasters have highlighted the need to prepare for subsets of critically ill, medically fragile patients. These special patient populations require focused disaster planning that will address their medical needs throughout the event to prevent clinical deterioration. The suggestions in this article are important for all who are involved in large-scale disasters or pandemics with multiple critically ill or injured patients, including frontline clinicians, hospital administrators, and public health or government officials. METHODS: Key questions regarding the care of critically ill or injured special populations during disasters or pandemics were identified, and a systematic literature review (1985-2013) was performed. No studies of sufficient quality were identified. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. The panel did not include pediatrics as a separate special population because pediatrics issues are embedded in each consensus document. RESULTS: Fourteen suggestions were formulated regarding the care of critically ill and injured patients from special populations during pandemics and disasters. The suggestions cover the following areas: defining special populations for mass critical care, special population planning, planning for access to regionalized service for special populations, triage and resource allocation of special populations, therapeutic considerations, and crisis standards of care for special populations. CONCLUSIONS: Chronically ill, technologically dependent, and complex critically ill patients present a unique challenge to preparing and implementing mass critical care. There are, however, unique opportunities to engage patients, primary physicians, advocacy groups, and professional organizations to lessen the impact of disaster on these special populations. © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS.
Stewart W.F.,Sutter Health |
Schwartz B.S.,00 North Academy Ave
Health and Place | Year: 2013
Coal abandoned mine lands (AMLs), persistent and prevalent across Pennsylvania, offer an instructive evaluation of potential contextual influences of chronic environmental contamination (CEC) on individual health. We evaluated associations between the burden of AMLs, represented by 10 contextual metrics at the community level, and individual-level type 2 diabetes using hemoglobin A1c (HbA1c) as a biomarker. Cross-sectional and longitudinal multilevel analyses were conducted with over 28,000 diabetic primary care patients of the Geisinger Clinic. Adjusted models revealed five AML burden measures were associated (p<0.05), and three additional were borderline associated (0.05≤. p≤0.10), with higher and/or change in HbA1c levels. This study provides key empirical evidence of adverse impacts of CEC in communities on an important chronic disease, illustrating the contextual effects of living in long-term degraded landscapes and communities. © 2013 Elsevier Ltd.
Arabi Y.M.,Riyadh |
Dara S.I.,Riyadh |
Tamim H.M.,King Abdullah International Medical Research Center |
Rishu A.H.,Riyadh |
And 11 more authors.
Critical Care | Year: 2013
Introduction: Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.Methods: We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.Results: Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).Conclusions: The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome. © 2013 Arabi et al.; licensee BioMed Central Ltd.
Kershenovich A.,00 North Academy Ave |
Macias O.M.,Hospital 20 Of Noviembre |
Macias O.M.,National Autonomous University of Mexico |
Syed F.,Geisinger Health System |
And 3 more authors.
Neurosurgery | Year: 2015
BACKGROUND: The estimated prevalence of lumbar or sacral transitional vertebrae (LSTV) in the population is 4% to 30%. Few small patient series have studied the normal level of the conus medullaris (CM) in individuals with LSTV. OBJECTIVE: To determine, by using a large cohort of patients, whether individuals of all ages with LSTV have different CM positions in the spinal canal in comparison with the rest of the population with normal vertebral columns. METHODS: We performed an institutional retrospective analysis of spinal magnetic resonance images on individuals with LSTV of all ages, sexes, and pathologies during a 10-year period. Fifty-seven percent of patients (n 467) had a lumbarized vertebra and 43% had sacralized vertebra (n 355). Mean age at the time of the study was 55 ± 19 years (range 1-97 years). Fifty-two percent were male and 48% were female. Sixty percent of subjects with a sacralized vertebra were female, and 54.5% of those with a lumbarized vertebra were male (P .001). RESULTS: The CM in individuals with a lumbarized vertebra was seen to be lower at L1-2 to L2s, than un those with a sacralized vertebra where most conuses were at T12-L1 to L1s (P ≤ 0.001). The CM level was similarly distributed among sexes and ages. CONCLUSION: In our series, the CM level, when lumbarization occurred, was lower, with a mean level at L1-L2, whereas a more superior mean level at T12-L1 was seen when sacralization occurred. CM level was not influenced by sex, age, or pathology other than tethered cords. © 2015 by the Congress of Neurological Surgeons.
Moore B.S.,00 North Academy Ave |
Mirshahi U.L.,00 North Academy Ave |
Ebersole T.L.,00 North Academy Ave |
Mirshahi T.,00 North Academy Ave
Journal of Biological Chemistry | Year: 2013
Ionotropic glutamate receptor (iGluR) channels control synaptic activity. The crystallographic structure of GluA2, the prototypical iGluR, reveals a clamshell-like ligand-binding domain (LBD) that closes in the presence of glutamate to open a gate on the pore lining α-helix. How LBD closure leads to gate opening remains unclear. Here, we show that bending the pore helix at a highly conserved alanine residue (Ala-621) below the gate is responsible for channel opening. Substituting Ala-621 with the smaller more flexible glycine resulted in a basally active, nondesensitizing channel with ∼39-fold increase in glutamate potency without affecting surface expression or binding. On GluA2(A621G), the partial agonist kainate showed efficacy similar to a full agonist, and competitive antagonists CNQX and DNQX acted as a partial agonists. Met-629 in GluA2 sits above the gate and is critical in transmitting LBD closure to the gate. Substituting Met-629 with the flexible glycine resulted in reduced channel activity and glutamate potency. The pore regions in potassium channels are structurally similar to iGluRs. Whereas potassium channels typically use glycines as a hinge for gating, iGluRs use the less flexible alanine as a hinge at a similar position to maintain low basal activity allowing for ligand-mediated gating. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Diehl D.L.,00 North Academy Ave |
Cheruvattath R.,00 North Academy Ave |
Facktor M.A.,Surgery Academy |
Go B.D.,00 North Academy Ave
Interactive Cardiovascular and Thoracic Surgery | Year: 2010
Foregut duplication cysts are rare congenital anomalies of enteric origin that arise during early embryonic development. They are usually incidentally found on routine imaging studies. The diagnosis can usually be made by computed tomography (CT) and endoscopic ultrasound (EUS) appearance. On CT, cyst attenuation values usually measure 0±20 Hounsfield units (HU). Higher HU is possible with hemorrhage, proteinaceous material or septations. At EUS, characteristic location and anechoic as well as hypoechoic but not necessarily anechoic appearance may be suggestive of a foregut duplication cyst. EUS-guided fine needle aspiration (FNA) has been thought to provide a safe, minimally invasive approach to establish the diagnosis. The purpose of this report is to highlight the potential for infectious risk of EUS-FNA for these cysts, and to suggest CT and EUS features that can suggest this diagnosis without FNA. Three patients who underwent EUS-FNA for diagnosis of incidental mediastinal lesions developed cyst infection despite accepted techniques including prophylactic antibiotics. Combined CT and EUS appearance may be sufficient in making this diagnosis without FNA. IV antibiotics may not be completely protective against infectious complications of FNA of mediastinal duplication cysts.
Elston D.M.,00 North Academy Ave
Current Opinion in Infectious Diseases | Year: 2010
Purpose of Review: Fever and a rash following a tick bite can signify a true medical emergency. Ticks are important vectors of disease worldwide, including Rocky Mountain spotted fever, Lyme disease, and Congo-Crimean hemorrhagic fever. This paper will review the major ticks of medical importance and the diseases they transmit, including important emerging pathogens. Recent Findings: Rocky Mountain spotted fever continues to be the most lethal tick-borne illness in the United States and is emerging as an important disease in South America. Other important emerging diseases include human anaplasmosis, southern tick associated rash illness, human monocytic ehrlichiosis, and a variety of rickettsial fevers including those caused by Rickettsia parkeri and Rickettsia amblyommii. Summary: Most tick-borne illnesses respond readily to doxycycline therapy. In the case of Rocky Mountain spotted fever, therapy should be started when the disease is suspected and should never be delayed for confirmatory tests. Accurate identification of tick vectors can help establish a diagnosis and can help guide preventive measures to reduce the burden of disease. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Venditti A.,00 North Academy Ave |
Ronk C.,00 North Academy Ave |
Kopenhaver T.,00 North Academy Ave |
Fetterman S.,Geisinger Health System
AACN Advanced Critical Care | Year: 2012
Tele-intensive care unit (ICU) technology has been proven to bridge the gap between available resources and quality care for many health care systems across the country. Tele-ICUs allow the standardization of care and provide a second set of eyes traditionally not available in the ICU. A growing body of literature supports the use of tele-ICUs based on improved outcomes and reduction in errors. To date, the literature has not effectively outlined the limitations of this technology related to response to changes in patient care, interventions, and interaction with the care team. This information can potentially have a profound impact on service expectations. Some misconceptions about tele-ICU technology include the following: tele-ICU is "watching" 24 hours a day, 7 days a week; tele-ICU is a telemetry unit; tele-ICU is a stand-alone crisis intervention tool; tele-ICU decreases staffing at the bedside; tele-ICU clinical roles are clearly defined and understood; and tele-ICUs are not cost-effective to operate. This article outlines the purpose of tele-ICU technology, reviews outcomes, and "busts" myths about tele-ICU technology. Copyright © 2012 American Association of Critical-Care Nurses.
Gogoi R.P.,00 North Academy Ave |
Urban R.,University of Washington |
Sun H.,00 North Academy Ave |
Goff B.,University of Washington
Gynecologic Oncology | Year: 2012
Objectives: The Society of Gynecologic Oncologists has developed two measures to assess and improve the surgical care of patients with ovarian cancer (1) description of residual disease following cytoreduction and (2) adequacy of surgical staging. Our aim was to establish baseline surgeon compliance with these two measures. Methods: A retrospective review of patients with ovarian, fallopian tube or peritoneal cancer undergoing surgery between 7/1/2006 and 7/1/2011 for the purposes of staging and/or cytoreduction was performed at the University of Washington and Geisinger Medical Center. Operative and pathology reports were reviewed to obtain information pertaining to stage, histology, residual disease after surgery and the extent of surgical staging. Results: 537 cases were identified; 91% with ovarian cancer. 61% of patients had at least stage IIIC disease; 15% had recurrent disease and 16% had neoadjuvant therapy. For patients with stages I-IIIB disease, 74% had full surgical staging, 10% did not have full surgical staging but documented the reason for this in the operative report; 15% did not have full surgical staging, no reason was noted. 25% of all operative reports lacked documentation of residual disease with 40% documenting no gross residual disease, 18% with residual disease < 1 cm and 18% had suboptimal debulking with > 1 cm disease remaining. There was a statistically significant increase in appropriate documentation of amount of residual disease over time (p < 0.001). Conclusions: Our study sets benchmarks for evaluation of documentation in gynecologic oncology centers. Improved documentation and staging will allow for equivalent standards of care across institutions. © 2012 Elsevier Inc. All rights reserved.