Hajar T.,Oregon Health And Science University |
Leshem Y.A.,Oregon Health And Science University |
Hanifin J.M.,Oregon Health And Science University |
Nedorost S.T.,University Hospital Case Medical Center |
And 4 more authors.
Journal of the American Academy of Dermatology | Year: 2015
Background The National Eczema Association has received increasing numbers of patient inquiries regarding "steroid addiction syndrome," coinciding with the growing presence of social media dedicated to this topic. Although many of the side effects of topical corticosteroids (TCS) are addressed in guidelines, TCS addiction is not. Objective We sought to assess the current evidence regarding addiction/withdrawal. Methods We performed a systematic review of the current literature. Results Our initial search yielded 294 results with 34 studies meeting inclusion criteria. TCS withdrawal was reported mostly on the face and genital area (99.3%) of women (81.0%) primarily in the setting of long-term inappropriate use of potent TCS. Burning and stinging were the most frequently reported symptoms (65.5%) with erythema being the most common sign (92.3%). TCS withdrawal syndrome can be divided into papulopustular and erythematoedematous subtypes, with the latter presenting with more burning and edema. Limitations Low quality of evidence, variability in the extent of data, and the lack of studies with rigorous steroid addiction methodology are limitations. Conclusions TCS withdrawal is likely a distinct clinical adverse effect of TCS misuse. Patients and providers should be aware of its clinical presentation and risk factors. © 2014 American Academy of Dermatology, Inc.
Patel V.N.,Case Western Reserve University |
Gokulrangan G.,Case Western Reserve University |
Chowdhury S.A.,Carnegie Mellon University |
Chen Y.,Case Western Reserve University |
And 4 more authors.
PLoS Computational Biology | Year: 2013
To determine a molecular basis for prognostic differences in glioblastoma multiforme (GBM), we employed a combinatorial network analysis framework to exhaustively search for molecular patterns in protein-protein interaction (PPI) networks. We identified a dysregulated molecular signature distinguishing short-term (survival<225 days) from long-term (survival>635 days) survivors of GBM using whole genome expression data from The Cancer Genome Atlas (TCGA). A 50-gene subnetwork signature achieved 80% prediction accuracy when tested against an independent gene expression dataset. Functional annotations for the subnetwork signature included "protein kinase cascade," "IκB kinase/NFκB cascade," and "regulation of programmed cell death" - all of which were not significant in signatures of existing subtypes. Finally, we used label-free proteomics to examine how our subnetwork signature predicted protein level expression differences in an independent GBM cohort of 16 patients. We found that the genes discovered using network biology had a higher probability of dysregulated protein expression than either genes exhibiting individual differential expression or genes derived from known GBM subtypes. In particular, the long-term survivor subtype was characterized by increased protein expression of DNM1 and MAPK1 and decreased expression of HSPA9, PSMD3, and CANX. Overall, we demonstrate that the combinatorial analysis of gene expression data constrained by PPIs outlines an approach for the discovery of robust and translatable molecular signatures in GBM. © 2013 Patel et al.
Nagaraj A.B.,Case Western Reserve University |
Joseph P.,Case Western Reserve University |
Kovalenko O.,Case Western Reserve University |
Singh S.,University Hospital Case Medical Center |
And 6 more authors.
Oncotarget | Year: 2015
Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/ß-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/ß-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/ß-catenin signaling is activated in ovarian CICs, and targeted inhibition of ß-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/ß-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/ß- catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.
Armstrong A.,University Hospital Case Medical Center |
Otvos B.,Case Western Reserve University |
Singh S.,University Hospital Case Medical Center |
Debernardo R.,University Hospital Case Medical Center
Gynecologic Oncology | Year: 2013
Objective Ovarian cancer accounts for 50% of deaths from gynecologic malignancies. We sought to determine the cost of common methods of surveillance of women with ovarian cancer in first clinical remission. The current standard for post treatment surveillance is the National Comprehensive Cancer Network (NCCN) guidelines. Methods We retrospectively determined how recurrence was initially detected at our institution and a cost model was created and applied to the United States population to calculate surveillance costs using the Surveillance Epidemiology & End Results (SEER) database. Results 57% (n = 60) of first recurrences were identified by increasing CA 125 level. Routine office visit identified 27% (n = 29) of recurrences, and 15% (n = 16) were diagnosed initially with CT scan. In 5% (5/105), CT abnormality was the only finding. 95% (100/105) of patients had either elevated CA 125 or office visit findings at time of recurrence. Of the 22,000 women diagnosed with ovarian cancer yearly, 60% (n = 13,266) will have advanced disease and are likely to recur. The surveillance cost for this population for 2 years using our model is $32,500,000 using NCCN guidelines and $58,000,000 if one CT scan is obtained. Conclusions Our data suggests that following NCCN guidelines will detect 95% of recurrences. An additional $26 million will be needed to identify the 5% of women with recurrence seen on CT only. Post treatment surveillance of ovarian cancer patients contributes significantly to health care costs. Use of CT scan to follow these patients largely increases cost with only a small increase in recurrence detection. © 2013 Elsevier Inc.
Li C.,Case Western Reserve University |
Xin W.,University Hospital Case Medical Center |
Sy M.-S.,Case Western Reserve University
Oncogene | Year: 2010
Over the last decades, cancer research has focused on tumor suppressor genes and oncogenes. Genes in other cellular pathways has received less attention. Between 0.5% to 1% of the mammalian genome encodes for proteins that are tethered on the cell membrane via a glycosylphosphatidylinositol (GPI)-anchor. The GPI modification pathway is complex and not completely understood. Prion (PrP), a GPI-anchored protein, is infamous for being the only normal protein that when misfolded can cause and transmit a deadly disease. Though widely expressed and highly conserved, little is known about the functions of PrP. Pancreatic cancer and melanoma cell lines express PrP. However, in these cell lines the PrP exists as a pro-PrP as defined by retaining its GPI anchor peptide signal sequence (GPI-PSS). Unexpectedly, the GPI-PSS of PrP has a filamin A (FLNA) binding motif and binds FLNA. FLNA is a cytolinker protein, and an integrator of cell mechanics and signaling. Binding of pro-PrP to FLNA disrupts the normal FLNA functions. Although normal pancreatic ductal cells lack PrP, about 40% of patients with pancreatic ductal cell adenocarcinoma express PrP in their cancers. These patients have significantly shorter survival time compared with patients whose cancers lack PrP. Pro-PrP is also detected in melanoma in situ but is undetectable in normal melanocyte, and invasive melanoma expresses more pro-PrP. In this review, we will discuss the underlying mechanisms by which binding of pro-PrP to FLNA disrupts normal cellular physiology and contributes to tumorigenesis, and the potential mechanisms that cause the accumulation of pro-PrP in cancer cells. © 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10.
Hecht C.R.,MetroHealth Medical Center |
Smith M.D.,MetroHealth Medical Center |
Radonich K.,Cleveland State University |
Kozlovskaya O.,John Carroll University |
Totten V.Y.,University Hospital Case Medical Center
Annals of Emergency Medicine | Year: 2011
Objective: This study compares and contrasts emergency department (ED) patient and staff attitudes towards ED-based HIV testing in 2 major hospitals in a single city, with an attempt to answer the following: Should routine ED-based HIV testing be offered? If so, who should be responsible for disclosing HIV test results? And what barriers might prevent ED-based HIV testing? Methods: Paper-based surveys were presented to a convenience sample of ED patients and staff at 2 urban, academic, tertiary care hospitals between December 2007 and June 2009. Descriptive statistics were derived with SAS and MicroSoft Excel. Data are reported in percentages, fractions, and graphs. Results: A total of 457 patients and 85 staff completed the surveys. The majority of patients favor ED-based HIV testing. Only a minority of ED staff support ED-based HIV testing. In both hospitals, patients prefer to have HIV test results delivered by a physician. This was true for both positive and negative results. However, only about one third of attending physicians feel comfortable disclosing a positive HIV test result. Patients and staff both view privacy and confidentiality as significant barriers to ED-based HIV testing. Conclusion: Although ED patients are overwhelmingly in favor of ED-based HIV testing, the staff is not. Patients and staff agree that physicians should deliver HIV test results to patients, but a significant number of physicians are not comfortable doing so. Historical barriers continue to hinder ED-based HIV testing programs. Copyright © 2011 by the American College of Emergency Physicians.
Saw J.,Vancouver General Hospital |
Bezerra H.,University Hospital Case Medical Center |
Gornik H.L.,Cleveland Clinic |
MacHan L.,Vancouver General Hospital |
Mancini G.B.J.,Vancouver General Hospital
Circulation | Year: 2016
Background-We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection. Angiographic manifestations of coronary FMD aside from dissection were considered rare. However, we observed several coronary FMD angiographic abnormalities with corresponding optical coherence tomography abnormalities. Methods and Results-Baseline demographics and imaging of patients with suspected coronary FMD at Vancouver General Hospital were reviewed. Presence of multifocal (string-of-beads) extracoronary FMD was confirmed by 2 specialists. In these patients, coronary angiographic findings (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for irregular stenosis, that is, stenosis with irregular borders in a focal or diffuse pattern with/without systolic accentuation; smooth stenosis, diffuse or focal; segmental dilatation/ectasia; and tortuosity. Optical coherence tomography was performed in a subset of patients. Of 32 patients with extracoronary FMD and suspected coronary involvement, 28 were women (88%), and their mean age was 59.4 ± 9.9 years. Nineteen presented with myocardial infarction (13 caused by spontaneous coronary artery dissection), and 13 had stable symptoms. The observed coronary angiographic abnormalities included tortuosity in all cases (91% were moderate to severe), irregular stenosis in 59%, smooth stenosis in 19%, and segmental dilatation/ectasia in 56%. Fifteen patients had optical coherence tomography of the abnormal segments showing abnormalities, including multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with thickening/accumulation of varied reflectivities, macrophage infiltration, loss/duplication of elastic membranes, and cavitation. Conclusions-This is the first case series describing findings suggestive of angiographic and intracoronary manifestations of coronary FMD. Future studies should prospectively review these features in patients with extracoronary FMD. © 2016 American Heart Association, Inc.
Guyuron B.,University Hospital Case Medical Center |
Guyuron B.,American Migraine Center |
Harvey D.,University Hospital Case Medical Center |
Harvey D.,American Migraine Center |
And 2 more authors.
Plastic and Reconstructive Surgery | Year: 2015
Background: The authors compared the reduction of migraine headache frequency, days, severity, and duration after surgical decompression versus avulsion of the zygomaticotemporal branch of the trigeminal nerve for treatment of temporal migraine headache. Methods: Twenty patients with bilateral temporal migraine headache were randomized to undergo avulsion of the zygomaticotemporal branch of the trigeminal nerve on one side and decompression via fasciotomy and removal of the zygomaticotemporal artery on the other side. Results were analyzed after a minimum of 12 months of follow-up. Results: Nineteen patients completed the study. The patients experienced greater than 50 percent improvement in frequency, migraine days, severity, and duration in 34 of the 38 operative sites (89 percent). Complete elimination of symptoms was noted in 21 of the 38 operative sites (55 percent). In the decompression group, migraine frequency was reduced from 14.6 to 2.2 per month, migraine days from 14.1 to 2.3, severity from 7.0 to 2.9, duration from 9.6 to 4.8 hours, and Migraine Headache Index score from 42 to 2.9. In the neurectomy group, frequency decreased from 14.2 to 1.9 per month, migraine days from 14.1 to 2.3, severity from 6.8 to 2.6, migraine duration from 10.1 to 5.3 hours, and the Migraine Headache Index score from 41 to 2.5. There was no statistical significance in reduced migraine headache frequency, days, severity, and duration between the two groups. Conclusions: Neurectomy and decompression of the zygomaticotemporal branch of the trigeminal nerve are both appropriate treatment for temporal migraine headache. If decompression fails to provide sufficient relief, neurectomy is another option. Copyright © 2015 by the American Society of Plastic Surgeons.
Bobanga I.D.,University Hospital Case Medical Center |
Barksdale E.M.,University Hospital Case Medical Center
European Journal of Pediatric Surgery | Year: 2016
Introduction We present the short- and long-term outcomes in the management of pure long-gap esophageal atresia (LGEA) using the Foker technique (FT) of esophageal elongation by external axial traction at a single institution. Methods All patients undergoing esophageal atresia (EA) repair with FT over a 10-year period were included in the study. Demographic data, birth weight, gestational age, associated anomalies, management, and short- and long-term outcomes were studied. Results Five patients (three males) were treated with FT in the study period, all with LGEA, with a mean birth weight of 1,926 g (range, 541-2,890 g). Four infants had associated anomalies. Primary repair after FT axial traction was achieved in four patients after a mean traction time of 13 days (range, 12-15 days). FT failed in one patient who had esophageal perforation from traumatic orogastric tube placement at birth and extensive matting of the esophagus at the time of FT attempt. The mean age at definitive esophageal anastomosis was 11.5 weeks (range, 8-14 weeks). In three of the five patients, traction sutures from the distal esophageal segment tore away, requiring a thoracotomy for replacement. One of the four patients had a confined leak at the anastomosis. All four patients developed strictures at the anastomosis, requiring serial dilations (mean 12 dilations, range 6-21 dilations), and three of those patients underwent a thoracotomy for stricture resection (two patients) or stricturoplasty (one patient). On long-term follow-up, all patients in whom a primary anastomosis was achieved had their gastrostomy closed and were on full oral feeds. Conclusion FT was successful in achieving a primary anastomosis in 80% of the patients with LGEA, with a significant morbidity but favorable long-term outcomes. © 2016 Georg Thieme Verlag KG Stuttgart. New York.
Gatherwright J.R.,University Hospital Case Medical Center |
Brown M.S.,University Hospital Case Medical Center |
Katira K.M.,University Hospital Case Medical Center |
Rowe D.J.,University Hospital Case Medical Center
Aesthetic Surgery Journal | Year: 2015
Background Three-dimensional (3D) changes in the midface following malar calcium hydroxyapatite (CaHa) injection have not been systematically analyzed. Objectives The authors analyzed 3D volume changes in midface and naso-labial fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease (NLC) junction following malar injection of CaHa in a cadaver model. Methods A single surgeon injected CaHa in the supraperiosteal plane. Sequential images were obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections. All measurements were performed by a single examiner. Injection location was verified anatomically. Results Injections were performed in 16 fresh cadaver hemi-faces. Maximal increases in projection were centered on the malar injection site, with associated decreases in projection and volume in the infero-medial locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed following the 1.5-cc and 3-cc injections, respectively. There was a relative decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3-cc injections, respectively. Injection of CaHa was associated with lateral movements of the NLF-NLC junction at the level of the nasal sill, philtral columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and 2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical dissection verified the location in the supraperiosteal space and within the middle malar fat pad. Conclusions Following malar CaHa injection, 3D photographic analysis showed a measureable lifting effect with recruitment of ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model. © 2015 The American Society for Aesthetic Plastic Surgery, Inc.