Zhou W.,Stanford University |
Zhou W.,Veterans Administration Palo Alto Health Care System |
Blay Jr. E.,Duke University |
Varu V.,Stanford University |
And 4 more authors.
Journal of Vascular Surgery | Year: 2014
Objective Endovascular aneurysm repair (EVAR) is considered the standard therapy for most patients with abdominal aortic aneurysm (AAA). Endoleak is a well-known EVAR-related complication that requires long-term follow-up. However, patient follow-up is often challenging outside clinical trials. We sought to evaluate the incidence and the effect of delayed endoleaks in a Veterans Administration (VA) health care system where long-term follow-up is ensured. Methods We retrospectively evaluated 213 consecutive patients who underwent EVAR at a referral Veterans Administration medical center. Age, aneurysm size, patency of lumbar and inferior mesenteric arteries, and follow-up evaluations were recorded. Type of endoleak, date of detection, and intervention were also documented. Patients who had <1 year of follow-up were excluded. The χ2 test, Student t-test, Mann-Whitney test, and Spearman correlation were used for data analysis. Results The analysis included 183 patients with a mean follow-up of 53 months (range, 12-141 months); of these, 48 patients (26%) had endoleaks, and 31 (17%) had aneurysm progression. The mean diagnosis time for nontype II (n = 14) endoleaks was 45 months (range, 3-127 months), and 71% were diagnosed >1 year after EVAR. All except one nontype II endoleak received prompt secondary interventions, and the one without intervention presented with aneurysm rupture. An isolated type II endoleak was detected in 34 patients at an average of 14.4 months (range, 0-76 months) after EVAR, 41% of which were detected >1 year after EVAR. Patients without a documented endoleak had a significant decrease in aneurysm size at the latest computed tomography evaluation compared to the preoperative size (4.8 vs 5.7 cm; P <.001), whereas those with isolated type II endoleak had an increase at the latest computed tomography follow-up compared to preoperative size (5.8 vs 5.7 cm). Importantly, 59% of the patients with a type II endoleak had significant AAA enlargement (0.8 cm), and delayed type II endoleak was significantly associated with sac enlargement compared to type II endoleaks detected early. No significant correlation was seen between the diameter of inferior mesenteric artery or lumbar to AAA enlargement among the patients with a type II endoleak. Secondary interventions in 12 patients with isolated type II endoleak resulted in overall aneurysm stabilization or regression. Conclusions This long-term outcome study demonstrated that delayed endoleaks appearing >1 year after EVAR contributed to most of the overall endoleaks and were significantly associated with aneurysm sac growth. This study underscores that type II endoleak is not benign and that vigilant lifelong surveillance after EVAR is critical. © 2014 by the Society for Vascular Surgery.
Giles J.T.,Columbia University |
Danoff S.K.,Johns Hopkins University |
Sokolove J.,Veterans Administration Palo Alto Health Care System |
Sokolove J.,Stanford University |
And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2014
Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown. Methods: RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantitative ILD Score (ILDS; range 0-32) were assessed. Anti-CCP (CCP2) and levels of a panel of antibodies against 17 citrullinated and four noncitrullinated peptides were assessed from concurrent serum samples using a custom Bio-Plex bead array. High level ACPA was defined as ≥the group 75th percentile. Results: Among the 177 RA patients studied, median levels of CCP2 and all specific ACPAs were 46-273% higher among RA patients with versus those without ILD (all p values <0.05), and higher levels correlated with higher ILDS. In contrast, levels of non-citrullinated protein antibodies were not higher in those with ILD. RA patients had a median of 2 high level ACPA reactivities (range 0-16), with each high level ACPA associated, on average, with a 0.10 unit higher ILDS (p=0.001). This association remained significant after adjusting for characteristics associated with ILD (age, gender, current and former smoking, Disease Activity Score for 28 joints, current prednisone and leflunomide use). More high level ACPA were observed in those with versus without pulmonary function restriction or impaired diffusion. Conclusions: Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.
Cockerham G.C.,Veterans Administration Palo Alto Health Care System |
Cockerham G.C.,Stanford University |
Lemke S.,Center for Health Care Evaluation |
Glynn-Milley C.,Veterans Administration Palo Alto Health Care System |
And 3 more authors.
Ocular Surface | Year: 2013
The pathophysiology of neurotrauma is reviewed and an original study investigating the prevalence of dry eye disease in a sample of veterans with traumatic brain injury (TBI) is presented. Fifty-three veterans with TBI were evaluated by history of injury, past ocular history, and medication use. Ocular Disease Surface Index (OSDI), ocular examination, cranial nerve evaluation, tear osmolarity, tear film break-up time (TFBUT), ocular surface staining and tear production testing were performed. A matched comparison group underwent similar testing. TBI causes were blast (44) or non-blast (9). TBI subjects scored significantly worse on the OSDI (P<.001), and ocular surface staining by Oxford scale (P<.001) than non-TBI subjects. Scores for tear film breakup (P=.6), basal tear production less than 3 mm (P=.13), and tear osmolarity greater than 314 mOsm/L (P=.15) were all higher in TBI subjects; significantly more TBI subjects had at least one abnormal dry eye measure than comparisons (P<.001). The OSDI related to presence of dry eye symptoms (P<.01). These effects were present in both blast and non-blast TBI. Seventy percent of TBI subjects were taking at least one medication in the following classes: antidepressant, atypical antipsychotic, anticonvulsant, or h1-antihistamine. There was no association between any medication class and the OSDI or dry eye measures. Reduced corneal sensation in 21 TBI subjects was not associated with OSDI, tear production, or TFBUT, but did correlate with reduced tear osmolarity (P=.05). History of refractive surgery, previous contact lens wear, facial nerve weakness, or meibomian gland dysfunction was not associated with DED. In summary, we found a higher prevalence of DED in subjects with TBI, both subjectively and objectively. This effect is unrelated to medication use, and it may persist for months to years. We recommend that patients with TBI from any cause be evaluated for DED using a battery of standard testing methods described in a protocol presented in this article. Further research into the pathophysiology and outcomes of DED in neurotrauma is needed. © 2013 Elsevier Inc.
Ueno M.,Veterans Administration Palo Alto Health Care System |
Ueno M.,Stanford University |
Shen W.-J.,Veterans Administration Palo Alto Health Care System |
Shen W.-J.,Stanford University |
And 6 more authors.
Journal of Lipid Research | Year: 2013
Fat-specifi c protein 27 (FSP27), a member of the cell death-inducing DNA fragmentation factor-like effector (Cide) family, is highly expressed in adipose tissues and is a lipid droplet (LD)-associated protein that induces the accumulation of LDs. Using a yeast two-hybrid system to examine potential interactions of FSP27 with other proteins, a direct interaction with the N-terminal region of nuclear factor of activated T cells 5 (NFAT5) was identifi ed. NFAT5 is a transcription factor that induces osmoprotective and infl ammatory genes after its translocation to the nucleus. The interaction between FSP27 and NFAT5 was confi rmed by bimolecular fl uorescence complementation and coimmunoprecipitation. Using immunocytochemistry, NFAT5 is detected in the cytoplasm and in the nucleus under isotonic conditions; however, overexpression of FSP27 inhibited the hypertonic-induced nuclear translocation of NFAT5. Consistent with the suppression of NFAT5 nuclear translocation, in cells transfected with a reporter construct containing the NFAT5 response element from the monocyte chemoattractant protein 1 (MCP1) promoter, FSP27 overexpression repressed hypertonic-induced luciferase activity and the expression of NFAT5 target genes. Knockdown of FSP27 in differentiated 3T3-L1 adipocytes increased the NFAT5-mediated rise in MCP1. These results suggest that FSP27 not only modulates LD homeostasis but also modulates the response to osmotic stress via a physical interaction with NFAT5 at the LD surface.Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc..
PubMed | University of Hawaii at Manoa, Veterans Administration Palo Alto Health Care System and Columbia University
Type: | Journal: Journal of the American Medical Informatics Association : JAMIA | Year: 2016
The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities.The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial.The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individuals health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients.
Flores-Figueroa E.,Instituto Mexicano Del Seguro Social |
Varma S.,Stanford University |
Montgomery K.,Stanford University |
Greenberg P.L.,Stanford University |
And 2 more authors.
Laboratory Investigation | Year: 2012
Mesenchymal stromal cells (MSCs) support hematopoiesis and are cytogenetically and functionally abnormal in myelodysplastic syndrome (MDS), implying a possible pathophysiologic role in MDS and potential utility as a diagnostic or riskstratifying tool. We have analyzed putative MSC markers and their relationship to CD34+ hematopoietic stem/progenitor cells (HSPCs) within intact human bone marrow in paraffin-embedded bone marrow core biopsies of benign, MDS and leukemic (AML) marrows using tissue microarrays to facilitate scanning, image analysis and quantitation. We found that CD271+, ALP+ MSCs formed an extensive branching perivascular, periosteal and parenchymal network. Nestin was brightly positive in capillary/arteriolar endothelium and occasional subendothelial cells, whereas CD146 was most brightly expressed in SMA+ vascular smooth muscle/pericytes. CD271+ MSCs were distinct by double immunofluorescence from CD163+ macrophages and were in close contact with but distinct from brightly nestin+ and from brightly CD146+ vascular elements. Double immunofluorescence revealed an intimate spatial relationship between CD34+ HSPCs and CD271+ MSCs; remarkably, 86% of CD34+ HSPCs were in direct contact with CD271+ MSCs across benign, MDS and AML marrows, predominantly in a perivascular distribution. Expression of the intercrine chemokine CXCL12 was strong in the vasculature in both benign and neoplastic marrow, but was also present in extravascular parenchymal cells, particularly in MDS specimens. We identified these parenchymal cells as MSCs by ALP/CXCL12 and CD271/CXCL12 double immunofluorescence. The area covered by CXCL12+ ALP+ MSCs was significantly greater in MDS compared with benign and AML marrow (P=0.021, Kruskal-Wallis test). The preservation of direct CD271+ MSC/CD34+ HSPC contact across benign and neoplastic marrow suggests a physiologically important role for the CD271+ MSC/CD34+ HSPC relationship and possible abnormal exposure of CD34+ HSPCs to increased MSC CXCL12 expression in MDS. © 2012 USCAP, Inc. All rights reserved.
Sahbaie P.,Veterans Administration Palo Alto Health Care System |
Sahbaie P.,Stanford University |
Li X.,Veterans Administration Palo Alto Health Care System |
Li X.,Stanford University |
And 4 more authors.
Anesthesiology | Year: 2012
BACKGROUND:: Neutrophils are one of the predominant immune cells initially migrating to surgical wound edges. They produce mediators both associated with supporting (interleukin [IL]-1β, C5a) and reducing (opioid peptides) pain. Studies demonstrate neutrophil depletion/blockade reduces nociceptive sensitization after nerve injury and carrageenan administration, but enhance sensitization in complete Freund's adjuvant inflammation. This research identifies the contribution of infiltrating neutrophils to incisional pain and inflammation. METHODS:: Antibody-mediated Gr1 neutrophil depletion preceded hind paw incisions. Sensitization to mechanical and thermal stimuli, effects on edema and local levels of IL-1β and C5a were measured. Local effects of C5a or IL-1 receptor antagonists PMX-53 and anakinra on sensitization after neutrophil depletion were examined. Groups of 4-8 mice were used. RESULTS:: Anti-Gr1 antibody depleted more than 90% of circulating and infiltrating skin neutrophils after incision. Neutrophil depletion did not change magnitude or duration of mechanical hypersensitivity in incised mice. However, paw edema was significantly reduced and heat hypersensitivity was slightly increased in depleted animals. In depleted animals IL-1β levels were half of controls 24 h after incision, whereas C5a levels were increased in both. Prominent IL-1β immunohistochemical staining of epidermis was seen in both groups. PMX-53 and anakinra reduced incisional mechanical and heat nociceptive sensitization to the same extent, regardless of neutrophil depletion. CONCLUSIONS:: Neutrophil-derived IL-1β and C5a do not appear to contribute critically to peri-incisional nociceptive signaling. Other sources of mediators, such as epidermal cells, may need to be considered. Controlling inflammatory activation of resident cells in epidermis/deeper structures may show therapeutic efficacy in reducing pain from surgical incisions. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.
Friedland S.,Veterans Administration Palo Alto Health Care System |
Friedland S.,Stanford University |
Kothari S.,Stanford University |
Chen A.,Stanford University |
And 2 more authors.
Gastrointestinal Endoscopy | Year: 2012
Background: Hyaluronic acid (HA) provides a long-lasting and distinct mucosal elevation for EMR, but expense and inconvenience have limited its adoption. Objective: To evaluate the safety and efficacy of an over-the-counter 0.15% HA preparation for EMR. Design: Retrospective study. Setting: Veterans Administration Hospital and university hospital. Patients: 30 patients with a total of 32 colonic lesions and 1 duodenal lesion. Intervention: EMR by using HA. Main Outcome Measurements: En bloc resection rate and complications. Results: EMR was successful in all cases. En bloc resection was achieved in 26 of the 28 lesions up to 25 mm in diameter. Two lesions, both with fibrosis from prior attempted resection, had trace residual tissue necessitating cauterization with argon plasma. Five lesions measuring 30 mm to 60 mm all required piecemeal resection. There was one complication, a postpolypectomy bleed. Limitations: Small number of patients and retrospective design. Conclusions: EMR may be performed safely and effectively by using an inexpensive, over-the-counter 0.15% HA preparation. Further studies are needed to verify the results of this study and to compare the safety and efficacy of this HA preparation with saline solution. © 2012 American Society for Gastrointestinal Endoscopy.
Nair V.S.,Stanford University |
Gevaert O.,Stanford University |
Davidzon G.,Stanford University |
Napel S.,Stanford University |
And 7 more authors.
Cancer Research | Year: 2012
Although 2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV max), SUV variance, and SUV PCA2], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis. ©2012 AACR.
Paulus Y.M.,Stanford University |
Cockerham G.C.,Stanford University |
Cockerham G.C.,Veterans Administration Palo Alto Health Care System
Journal of Ophthalmic Inflammation and Infection | Year: 2013
Background: Infectious crystalline keratopathy is commonly caused by Streptococcus viridans and other gram positive organisms. We present the first case of infectious crystalline keratopathy that developed into a corneal ulcer and grew Abiotrophia defectiva which responded well to topical and systemic antimicrobial therapy and did not require re-grafting. A 78-year-old man underwent penetrating keratoplasty for pseudophakic bullous keratopathy. He presented 1.5 years later with infectious crystalline keratopathy which progressed to a corneal ulcer. The patient received topical fortified vancomycin and moxifloxacin, as well as oral moxifloxacin. Findings: The corneal ulcer base was cultured and grew A. defectiva, or nutritionally deficient streptococcus. Complete resolution of the corneal infiltrates was obtained within three months. Conclusions: Nutritionally deficient streptococcus has been implicated in numerous human diseases, including endocarditis, and is increasingly being recognized as an important pathogen. This represents the second reported case of A. defectiva causing infectious crystalline keratopathy in humans and the first case of A. defectiva successfully treated with antibiotics. This case shows that aggressive antibiotic therapy can be effective in A. defectiva-associated infectious crystalline keratopathy. © 2013 Paulus and Cockerham.