Medicine, Department of

Utility of Intraoperative Frozen Section Histopathology in the Diagnosis of Periprosthetic Joint Infection

Sat, 01 Sep 2012 05:00:00 GMT

Utility of Intraoperative Frozen Section Histopathology in the Diagnosis of Periprosthetic Joint Infection Tsaras, Geoffrey; Maduka-Ezeh, Awele; Inwards, Carrie Y.; Mabry, Tad; Erwin, Patricia J.; Murad, Hassan; Montori, Victor M.; West, Colin P.; Osmon, Douglas R.; Berbari, Elie F. Background: The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown. Methods: We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010. Results: Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined. Conclusions: Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culturepositive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per highpower field. This is a copy of an article published in the Journal of Bone and Joint Surgery, American Volume © 2012 Journal of Bone and Joint Surgery, Inc DOI: 10.2106/JBJS.J.00756

Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia

Sun, 01 Jan 2012 06:00:00 GMT

Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia Bhattacharyya, Sumit; Tobacman, Joanne K. This report presents evidence of 1) a role for arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in mediating intracellular oxygen signaling; 2) replication between the effects of ARSB silencing and hypoxia on sulfated glycosaminoglycan content, cellular redox status, and expression of hypoxia-associated genes; and 3) a mechanism whereby changes in chondroitin-4-sulfation that follow either hypoxia or ARSB silencing can induce transcriptional changes through galectin-3. ARSB removes 4-sulfate groups from the non-reducing end of chondroitin-4-sulfate and dermatan sulfate and is required for their degradation. For activity, ARSB requires modification of a critical cysteine residue by the formylglycine generating enzyme and by molecular oxygen. When primary human bronchial and human colonic epithelial cells were exposed to 10% O261 h, ARSB activity declined by ,41% and ,30% from baseline, as nuclear hypoxia inducible factor (HIF)-1a increased by ,53% and ,37%. When ARSB was silenced, nuclear HIF-1a increased by ,81% and ,61% from baseline, and mRNA expression increased to 3.73 (60.34) times baseline. Inversely, ARSB overexpression reduced nuclear HIF-1a by ,37% and ,54% from baseline in the epithelial cells. Hypoxia, like ARSB silencing, significantly increased the total cellular sulfated glycosaminoglycans and chondroitin-4-sulfate (C4S) content. Both hypoxia and ARSB silencing had similar effects on the cellular redox status and on mRNA expression of hypoxia-associated genes. Transcriptional effects of both ARSB silencing and hypoxia may be mediated by reduction in galectin-3 binding to more highly sulfated C4S, since the galectin-3 that co-immunoprecipitated with C4S declined and the nuclear galectin-3 increased following ARSB knockdown and hypoxia. This is a copy of an article published in PLoS ONE by the Public Library of Science. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. doi:10.1371/journal.pone.0033250

Increased mortality among publicly insured participants in the HIV Outpatient Study despite HAART treatment.

Sat, 24 Sep 2011 05:00:00 GMT

Increased mortality among publicly insured participants in the HIV Outpatient Study despite HAART treatment. Palella, FJ Jr; Baker, RK; Buchacz, K; Chmiel, JS; Tedaldi, EM; Novak, RM; Durham, MD; Brooks, JT Objective: Understanding mortality differences among HIV-infected patients can focus efforts to improve survival. Design: We evaluated death rates, causes and associated factors among treated patients in the HOPS, a large, prospective, multicenter observational cohort of HIV-infected persons seen at diverse U.S. sites of care. Methods: Among 3754 HOPS participants seen during 1996-2007 with > 6 months of follow-up after initiating HAART and ≥ 75% of time under observation receiving HAART (“substantially treated”), we calculated hazard ratios for death using proportional hazards regression models, death causes and comorbidities. Results: Substantially treated participants, followed a median 4.7 years (IQR, 2.2-8.5), experienced 331 deaths. In multivariable analyses, higher mortality was associated with index CD4 < 200 counts/mm3 (adjusted hazard ratio [aHR], 2.86; 95% CI, 1.95-4.21), older age (aHR, 1.50 per 10 years; 95% CI, 1.33-1.70), log10HIV RNA (aHR, 1.67 per log10; 95% CI, 1.51-1.85), but not race/ethnicity (aHR, 0.99 for blacks vs whites, p=0.92). Mortality was increased among publicly insured (PUB) vs privately insured participants (PRV ) when index CD4 >200 (aHR, 2.03; 95% CI, 1.32-3.14) but not when index CD4 < 200 cells/mm3 (aHR, 1.3, p=0.13). By death cause, PUB had significantly more cardiovascular events and hepatic disorders than PRV. Comorbidities more frequent among PUB vs PRV decedents included cardiovascular disease, renal impairment and chronic hepatitis. Conclusions: Among HAART treated participants with CD4 ≥ 200 cells/mm3, PUB experienced higher death rates than PRV. Non-AIDS death and disease causes predominated among publicly insured decedents, suggesting that treatable comorbidities contributed to survival disparities. Post print version of article may differ from published version. The definitive version is available through Lippincott, Williams & Wilkins at DOI:10.1097/QAD.0b013e32834b3537

Permissiveness of human hepatoma cell lines for HCV infection

Sun, 01 Jan 2012 06:00:00 GMT

Permissiveness of human hepatoma cell lines for HCV infection Sainz Jr, Bruno; Barretto, Naina; Yu, Xuemei; Corcoran, Peter; Uprichard, Susan L Background: Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culturederived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). Results: We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. Conclusions: We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection. © 2011 Sainz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1186/1743-422X-9-30