PMID- 29529651 OWN - NLM STAT- MEDLINE DCOM- 20190314 LR - 20200306 IS - 1528-1132 (Electronic) IS - 0009-921X (Print) IS - 0009-921X (Linking) VI - 476 IP - 2 DP - 2018 Feb TI - Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs. PG - 230-241 LID - 10.1007/s11999.0000000000000028 [doi] AB - BACKGROUND: Once touted as the future of hip arthroplasty, metal-on-metal (MoM) bearing surfaces have fallen sharply from favor with the emergence of a strong body of evidence demonstrating unacceptably high premature implant failure rates. The previously unpredictable development of adverse local tissue reactions (ALTRs) has been a substantive contributor to this. Although the underlying pathophysiology of these so-called "pseudotumors" is now well understood, the fundamental predisposing patient risk factors have remained elusive. QUESTIONS/PURPOSES: The aim of this research, as a clinical-genotype correlation analysis, was to identify specific alleles (genes) associated with the development of ALTRs in patients with in situ MoM THAs. METHODS: A case-control study of patients who received a large-head, primary MoM THA between 2005 and 2008 was performed with a minimum followup of 5 years. Twenty-six patients who had undergone revision of a primary MoM THA secondary to symptomatic ALTRs were recruited. The mean timeframe from primary MoM THA to symptomatic revision was 5.5 years (range, 1-10 years). Twenty-eight control subjects were randomly selected asymptomatic patients with no evidence of ALTRs on protocol-specific screening. Baseline demographics and high-resolution genotype (human leukocyte antigen [HLA] Class II) were collected for all patients. Cohorts were similar with respect to age at the time of primary MoM THA (mean, 54.8 versus 54.9 years, p = 0.95) and serum cobalt (mean, 5.5 versus 8.5 mug/L, p = 0.09) and chromium concentrations (mean, 2.9 versus 4.2 mug/L, p = 0.27). The association between genotype and revision surgery secondary to ALTRs was determined with gender as a covariate. RESULTS: The prevalence of the risk genotype was 30% (16 of 54) among the entire cohort. Adjusting for sex, the odds of revision were 6.1 times greater among patients with the risk genotype present than among patients without (95% confidence interval [CI], 1.5-25.4; p = 0.01). Among females, the specificity of the risk genotype was 1.0 (95% CIexact, 0.5-1.0; pexact = 0.03), and for males, it was 0.8 (95% CIexact, 0.6-0.9; pexact < 0.01). CONCLUSIONS: The findings of this study suggest that, among patients with a primary MoM THA, allelic variation within the HLA Class II loci may be a strong, independent risk factor associated with the need for subsequent revision surgery secondary to pseudotumor formation. CLINICAL RELEVANCE: Given the hypothesis-generating nature of this novel undertaking, confirmatory prospective clinical studies are required to further elucidate this correlation and to explore the clinical utility of targeted genetic screening in this specific population. This research may, however, represent a key missing piece in the puzzle that is metal ion-induced pseudotumor formation. FAU - Kilb, Brett K J AU - Kilb BKJ AD - B. K. J. Kilb, A. P. Kurmis, M. Parry, B. A. Masri, C. P. Duncan, D. S., Garbuz Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada K. Sherwood, P. Keown Department of Pathology (&) Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada P. Keown, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada A. P. Kurmis, Discipline of Medical Specialties, University of Adelaide, Adelaide, SA, Australia. FAU - Kurmis, Andrew P AU - Kurmis AP FAU - Parry, Michael AU - Parry M FAU - Sherwood, Karen AU - Sherwood K FAU - Keown, Paul AU - Keown P FAU - Masri, Bassam A AU - Masri BA FAU - Duncan, Clive P AU - Duncan CP FAU - Garbuz, Donald S AU - Garbuz DS LA - eng PT - Journal Article PL - United States TA - Clin Orthop Relat Res JT - Clinical orthopaedics and related research JID - 0075674 RN - 0 (Histocompatibility Antigens Class II) SB - IM CIN - Clin Orthop Relat Res. 2018 Feb;476(2):242-244. PMID: 29529652 MH - Aged MH - Arthroplasty, Replacement, Hip/*adverse effects/*instrumentation MH - British Columbia/epidemiology MH - Case-Control Studies MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Granuloma, Plasma Cell/epidemiology/*genetics/immunology/surgery MH - Hip Joint/physiopathology/*surgery MH - *Hip Prosthesis MH - Histocompatibility Antigens Class II/*genetics/immunology MH - Humans MH - Male MH - *Metal-on-Metal Joint Prostheses MH - Middle Aged MH - Prevalence MH - Prosthesis Design MH - *Prosthesis Failure MH - Reoperation MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome PMC - PMC6259707 COIS- Each author certifies that neither he or she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research((R)) editors and board members are on file with the publication and can be viewed on request. EDAT- 2018/03/13 06:00 MHDA- 2019/03/15 06:00 PMCR- 2019/02/01 CRDT- 2018/03/13 06:00 PHST- 2018/03/13 06:00 [entrez] PHST- 2018/03/13 06:00 [pubmed] PHST- 2019/03/15 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - 00003086-201802000-00013 [pii] AID - CORR-D-16-01581 [pii] AID - 10.1007/s11999.0000000000000028 [doi] PST - ppublish SO - Clin Orthop Relat Res. 2018 Feb;476(2):230-241. doi: 10.1007/s11999.0000000000000028.