Providence Sacred Heart Medical Center and Childrens Hospital

Spokane, WA, United States

Providence Sacred Heart Medical Center and Childrens Hospital

Spokane, WA, United States

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Riviere J.-B.,Seattle Childrens Hospital | Mirzaa G.M.,University of Chicago | O'Roak B.J.,University of Washington | Beddaoui M.,University of Ottawa | And 36 more authors.
Nature Genetics | Year: 2012

Megalencephaly-capillary malformation (MCAP) and megalencephaly- polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism. © 2012 Nature America, Inc. All rights reserved.


Tuttle K.R.,Providence Sacred Heart Medical Center and Childrens Hospital | Tuttle K.R.,University of Washington | Tuot D.S.,University of California at San Francisco | Corbett C.L.,Providence Sacred Heart Medical Center and Childrens Hospital | And 4 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2013

Strategies to effectively treat people with CKD have been identified by conventional clinical research. Despite this evidence, awareness, screening, detection, diagnosis, risk factor control, treatment, and outcomes remain substandard. Translating clinical evidence into actionable measures that reduce the burden of CKD is a pressing need. Expansion from a "bench-to-bedside" paradigm (conventional type 1 translation) to research that encompasses "clinic and community" is the core concept of type 2 translation. Specifically, this is the discipline of identifying factors and using strategies that lead to adoption, maintenance, and sustainability of science-based interventions in practice. This review identifies key elements of type 2 translational research and highlights the current scope of this type of research for CKD. For type 2 translation to achieve the goals of providing high-quality care and better health outcomes, key facilitators (e.g., theory-based frameworks, adaptable interventions, and inclusion of sustainability and evaluation metrics) and essential elements (e.g., multidisciplinary team care, health information technology, and stakeholder engagement) must be integrated. The National Institute of Diabetes and Digestive and Kidney Diseases recently funded five proposals that aim to improve outcomes for people with CKD, focusing on diverse components of the healthcare continuum: patient safety and transitions; delivery of highquality, evidence-based CKD care; and elimination of disparities. The need for type 2 translational research in CKD is urgent because of preventable human suffering and unsustainable costs of providing care. Focus on the theory, framework, and approaches we have suggested may help us meet that challenge. © 2013 by the American Society of Nephrology.


Brott T.G.,Mayo Medical School | Howard G.,University of Alabama at Birmingham | Roubin G.S.,Cardiovascular Asso. of the Southeast | Meschia J.F.,Mayo Medical School | And 15 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND In the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during 4 years of follow-up. We now extend the results to 10 years. METHODS Among patients with carotid-artery stenosis who had been randomly assigned to stenting or endarterectomy, we evaluated outcomes every 6 months for up to 10 years at 117 centers. In addition to assessing the primary composite end point, we assessed the primary end point for the long-term extension study, which was ipsilateral stroke after the periprocedural period. RESULTS Among 2502 patients, there was no significant difference in the rate of the primary composite end point between the stenting group (11.8%; 95% confidence interval [CI], 9.1 to 14.8) and the endarterectomy group (9.9%; 95% CI, 7.9 to 12.2) over 10 years of follow-up (hazard ratio, 1.10; 95% CI, 0.83 to 1.44). With respect to the primary long-term end point, postprocedural ipsilateral stroke over the 10-year follow-up occurred in 6.9% (95% CI, 4.4 to 9.7) of the patients in the stenting group and in 5.6% (95% CI, 3.7 to 7.6) of those in the endarterectomy group; the rates did not differ significantly between the groups (hazard ratio, 0.99; 95% CI, 0.64 to 1.52). No significant between-group differences with respect to either end point were detected when symptomatic patients and asymptomatic patients were analyzed separately. CONCLUSIONS Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups. (Funded by the National Institutes of Health and Abbott Vascular Solutions; CREST ClinicalTrials.gov number, NCT00004732.) © Copyright 2016 Massachusetts Medical Society. All rights reserved.


De Marchena E.,University of Miami | Mesa J.,University of Miami | Pomenti S.,University of Miami | Marin Y Kall C.,University of Miami | And 9 more authors.
JACC: Cardiovascular Interventions | Year: 2015

Objectives This paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy. Background Only a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis. Methods Through reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments. Results This paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully. Conclusions These 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure. © 2015 American College of Cardiology Foundation.


Felgenhauer J.L.,Providence Sacred Heart Medical Center and Childrens Hospital | Nieder M.L.,All Childrens Hospital | Krailo M.D.,University of Southern California | Bernstein M.L.,Health Center | And 8 more authors.
Pediatric Blood and Cancer | Year: 2013

Background: The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data. Procedures: Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide. Vinblastine and celecoxib were concomitantly administered. Surgical, radiotherapeutic, or combination local control therapy was given per institutional preference. Results: Thirty-five eligible patients were enrolled. Ninety percent received at least 75% of planned vinblastine/celecoxib doses. There was no excess of neurologic, infectious, hemorrhagic, or cardiovascular toxicities. However, 7 of 21 patients who received pulmonary irradiation prior to experiencing pulmonary toxicity did develop grade 2 or greater pulmonary toxicity, including two deaths of apparent radiation pneumonitis. Fourteen of 16 patients with pelvic disease received local irradiation. Hemorrhagic cystitis developed in six patients, five of whom had received pelvic irradiation. The overall 24-month event free survival was 35% (19-51%); 71% (26-92%) for the seven with isolated pulmonary metastases, 26% (10-45%) for all others. Conclusion: The combination of vinblastine/celecoxib metronomic therapy with standard ES treatment was feasible according to the protocol definitions. However, excess toxicity in irradiated areas was noted and limits the usefulness of this protocol. The 24-month EFS for those with isolated pulmonary metastases is better than historical controls, although the number of patient number is small, follow up short and we are lacking contemporaneous controls. © 2012 Wiley Periodicals, Inc.


Murphy S.M.,Washington State University | Neven D.,Providence Sacred Heart Medical Center and Childrens Hospital
Journal of Emergency Medicine | Year: 2014

Background Frequent and unnecessary utilization of the emergency department (ED) is often a sign of serious latent patient issues, and the associated costs are shared by many. Helping these patients get the care they need in the appropriate setting is difficult given their complexity, and their tendency to visit multiple EDs. Study Objective We analyzed the cost-effectiveness of a multidisciplinary ED-care-coordination program with a regional hospital information system capable of sharing patients' individualized care plans with cooperating EDs. Methods ED visits, treatment costs, cost per visit, and net income were assessed pre- and postenrollment in the program using nonparametric bootstrapping techniques. Individuals were categorized as frequent (3-11 ED visits in the 365 days preceding enrollment) or extreme (≥ 12 ED visits) users. Regression to the mean was tested using an adjusted measure of change. Results Both frequent and extreme users experienced significant decreases in ED visits (5 and 15, respectively; 95% confidence intervals [CI] 2-5 and 13-17, respectively) and direct-treatment costs ($1285; 95% CI $492-$2364 and $6091; 95% CI $4298-$8998, respectively), leading to significant hospital cost savings and increased net income ($431; 95% CI $112-$878 and $1925; 95% CI $1093-$3159, respectively). The results further indicate that fewer resources were utilized per visit. Regression to the mean did not seem to be an issue. Conclusions When examined as a whole, research on the program suggests that expanding it would be an efficient allocation of hospital, and possibly societal, resources. © 2014 Elsevier Inc.


Alicic R.Z.,University of Washington | Alicic R.Z.,Providence Sacred Heart Medical Center and Childrens Hospital | Alicic R.Z.,Providence Medical Research Center | Patakoti R.,University of Washington | And 5 more authors.
Advances in Chronic Kidney Disease | Year: 2013

Over the last few decades, much of the world has experienced an epidemic of obesity. In the year 2008, 1.4 billion people worldwide were overweight, and 500 million were obese. Even more alarming is a fact that in the year 2010, 40 million children under the age of 5 years were overweight or obese. In the same time period, the incidence of CKD has also increased worldwide. Obesity has been recognized as a driving force of another global epidemic-diabetes, the leading cause of ESRD. Recent studies are confirming that in addition to risk associated with diabetes per se, increased body mass index is independently linked to increased risk for various kidney disorders, prominently CKD, but also renal cell carcinoma and nephrolithiasis. The purpose of this article is to review current knowledge regarding adverse effects of obesity on the kidney. © 2013 National Kidney Foundation, Inc.


Alicic R.Z.,Providence Sacred Heart Medical Center and Childrens Hospital | Alicic R.Z.,University of Washington | Tuttle K.R.,Providence Sacred Heart Medical Center and Childrens Hospital | Tuttle K.R.,University of Washington
Advances in Chronic Kidney Disease | Year: 2014

The number of people diagnosed with diabetes is rising throughout the world, which in turn drives upward the global frequency of diabetic kidney disease (DKD). Individuals with DKD are at an increased risk for premature death, cardiovascular disease, and other severe illnesses that result in frequent hospitalizations and increased health-care utilization. Current treatments concentrate on controlling hyperglycemia and hypertension with the specific use of renin-angiotensin system inhibitors. Although such measures reduce the risk of progressive kidney disease, DKD remains the leading cause of ESRD and the major risk amplifier for death in this population. Therefore, novel therapeutic approaches are urgently needed. Ideas for novel targets for therapy are founded on recent advances in understanding DKD mechanisms that are based on experimental models and human observations. The purpose of this review is to describe the epidemiology and present knowledge of DKD pathophysiology as the basis for novel therapies including inhibitors of Janus kinases (JAK), protein kinase C, fibrosis, advanced glycation end products treatments, and endothelin. © 2014 National Kidney Foundation, Inc.


Raabe R.D.,Providence Sacred Heart Medical Center and Childrens Hospital | Burr R.B.,Providence Sacred Heart Medical Center and Childrens Hospital | Short R.,Providence Sacred Heart Hospital
Journal of Vascular and Interventional Radiology | Year: 2010

Purpose: To assess relatively long-term (ie, 1 year) neurocognitive outcomes of patients undergoing carotid artery stent (CAS) placement with cerebral protection. Materials and Methods: Sixty-two patients (19 symptomatic; mean age, 73 years) with significant carotid stenosis (≥ 70% for symptomatic patients, ≥ 80% for asymptomatic patients) underwent CAS placement with embolic protection. Cognitive function was assessed prospectively with use of a battery of standardized tests administered at baseline (1-5 days before CAS endovascular therapy) and at 3, 6, and 12 months after CAS placement. Diffusion-weighted imaging (DWI) was performed before the procedure and within 24 hours after CAS placement. Results: Results of statistical modeling across occasions of measurement indicated significant main effects of occasion for the Dementia Rating Scale (DRS)-2 concept formation (P < .001), memory (P = .029), and total scores (P = .001); the DRS-2 total age- and education-corrected Mayo Older Americans Normative Studies score (P < .001); and the North American Adult Reading Test IQ score (P = .003). The vast majority of patients showed improvement or no change relative to baseline DRS-2 total scores at all time points. No significant relationship between DWI outcomes and cognition scores over time was found. Age influenced improvement on cognitive tests, whereas baseline symptom status did not. Conclusions: Revascularization with a carotid stent and neuroprotection, at a minimum, left cognitive function unchanged in patients receiving a CAS, and in many instances improved it. The preliminary findings of this prospective pilot study should be confirmed with a larger, controlled trial. © 2010 SIR.

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