Impact of Acetabular Implant Design on Aseptic Failure in Total Hip Arthroplasty.

BACKGROUND: Failure of cementless acetabular osseointegration is rare in total hip arthroplasty. Nevertheless, new fixation surfaces continue to be introduced. Novel implants may lack large diameter, constrained bearings, or dual mobility (DM) bearings to address instability. We compared clinical and radiographic outcomes for acetabular components with differing fixation surfaces and bearing options, focusing on the relationship between fixation surface and osseointegration and the relationship between bearing options and dislocation rate. METHODS: We retrospectively reviewed 463 total hip arthroplasties implanted with 3 different acetabular components between 2012 and 2016. Records were reviewed for demographics, clinical scores, and complications. Radiographs were examined for evidence of acetabular osteointegration. Analysis of variance and chi-square tests were used to compare cohorts. RESULTS: All cohorts had 100% survivorship free of acetabular fixation failure with no differences in clinical scores. Dislocation occurred in 1.3% of cases (n = 6). Analysis of the "transition" sizes, for which brand determined the maximum bearing diameter, revealed a significantly higher dislocation rate (3/50, 6%) in implants with limited bearing options. All 4 revisions for recurrent dislocation involved well-positioned components that did not accept large diameter, constrained bearings, or DM bearings, resulting in 3 shell revisions to expand bearing options. Femoral revisions were associated with dislocation risk but did not vary between cohorts. CONCLUSION: Dislocation was the primary mechanical cause for acetabular revision, while acetabular fixation failure was not encountered. We caution against selecting "new and improved" acetabular components without options for large diameter, constrained bearings, or DM bearings, even when enabling technology makes component positioning reliable.

Evaluating the Quality, Accuracy, and Readability of Online Resources Pertaining to Hallux Valgus.

BACKGROUND: The Internet is one of the most widely utilized resources for health-related information. Evaluation of the medical literature suggests that the quality and accuracy of these resources are poor and written at inappropriately high reading levels. The purpose of our study was to evaluate the quality, accuracy, and readability of online resources pertaining to hallux valgus. METHODS: Two search terms ("hallux valgus" and "bunion") were entered into Google, Yahoo, and Bing. With the use of scoring criteria specific to hallux valgus, the quality and accuracy of online information related to hallux valgus was evaluated by 3 reviewers. The Flesch-Kincaid score was used to determine readability. Statistical analysis was performed with t tests and significance was determined by P values <.05. RESULTS: Sixty-two unique websites were evaluated. Quality was significantly higher with use of the search term "bunion" as compared to "hallux valgus" (P = .045). Quality and accuracy were significantly higher in resources authored by physicians as compared to nonphysicians (quality, P = .04; accuracy, P < .001) and websites without commercial bias (quality, P = .038; accuracy, P = .011). However, the reading level was significantly more advanced for websites authored by physicians (P = .035). Websites written above an eighth-grade reading level were significantly more accurate than those written at or below an eighth-grade reading level (P = .032). CONCLUSION: The overall quality of online information related to hallux valgus is poor and written at inappropriate reading levels. Furthermore, the search term used, authorship, and presence of commercial bias influence the value of these materials. It is important for orthopaedic surgeons to become familiar with patient education materials, so that appropriate recommendations can be made regarding valuable resources. LEVELS OF EVIDENCE: Level IV.

MRI for the evaluation of knee pain: comparison of ordering practices of primary care physicians and orthopaedic surgeons.

BACKGROUND: Knee pain is one of the most common reasons for outpatient visits in the U.S. The great majority of such cases can be effectively evaluated through physical examination and judicious use of radiography. Despite this, an increasing number of magnetic resonance images (MRIs) of the knee are being ordered for patients with incomplete work-ups or for inappropriate indications. We hypothesized that MRIs ordered by orthopaedic providers were more likely to result in changes in diagnoses and/or plans for care than those ordered by non-orthopaedic providers. METHODS: We reviewed the charts of all consecutive new patients seen at our orthopaedic outpatient office between January 1, 2010, and December 31, 2011, with International Classification of Diseases, Ninth Revision (ICD-9) codes for meniscal or unspecific sprains and strains of the knee. A total of 1592 patients met our inclusion criteria and were divided into two groups: those initially evaluated and referred by their primary care physician (PCP) (n = 747) and those initially evaluated by one of our staff orthopaedic surgeons (n = 845). RESULTS: MRI-ordering rates were nearly identical between orthopaedic surgeons and PCPs (25.0% versus 24.8%; p = 0.945). MRIs ordered by orthopaedic surgeons, however, resulted in significantly more arthroscopic interventions than those ordered by PCPs (41.2% versus 31.4%; p = 0.042). Orthopaedic surgeons ordered MRIs for patients who were more likely to benefit from arthroscopic intervention, including patients who were younger (mean age, 45.1 years versus 56.5 years for those with PCP-ordered MRIs; p < 0.001), patients with acute symptoms (39.3% versus 22.2%; p < 0.001), and patients with a history of trauma (49.3% versus 36.2%; p = 0.019). Finally, orthopaedic surgeons were less likely than PCPs to order MRIs for patients with substantial osteoarthritis who subsequently underwent total knee arthroplasty (4.3% versus 9.2%; p = 0.048). CONCLUSIONS: MRI utilization by orthopaedic surgeons results in more appropriate interventions for patients with symptoms and findings most amenable to surgical intervention.

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice.

We have considered a novel gene targeting approach for treating pathologies and conditions whose genetic bases are defined using diet and nutrition. One such condition is Down syndrome, which is linked to overexpression of RCAN1 on human chromosome 21 for some phenotypes. We hypothesize that a decrease in RCAN1 expression with dietary supplements in individuals with Down syndrome represents a potential treatment. Toward this, we used in vivo studies and bioinformatic analysis to identify potential healthy dietary RCAN1 expression modulators. We observed Rcan1 isoform 1 (Rcan1-1) protein reduction in mice pup hippocampus after a 4-week curcumin and fish oil supplementation, with only fish oil reduction being statistically significant. Focusing on fish oil, we observed a 17% Rcan1-1 messenger RNA (mRNA) and 19% Rcan1-1 protein reduction in BALB/c mice after 5 weeks of fish oil supplementation. Fish oil supplementation starting at conception and in a different mouse strain (C57BL) led to a 27% reduction in hippocampal Rcan1-1 mRNA and a 34% reduction in spleen Rcan1-1 mRNA at 6 weeks of age. Hippocampal protein results revealed a modest 11% reduction in RCAN1-1, suggesting translational compensation. Bioinformatic mining of human fish oil studies also revealed reduced RCAN1 mRNA expression, consistent with the above studies. These results suggest the potential use of fish oil in treating Down syndrome and support our strategy of using select healthy dietary agents to treat genetically defined pathologies, an approach that we believe is simple, healthy, and cost-effective.

Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment.

OBJECTIVES: Recent evidence supports the involvement of RCAN1 in Down syndrome and Alzheimer's disease. To better assess this, we generated and analyzed transgenic mice overexpressing human RCAN1 isoform 4 in neurons. METHODS: Cognitive behavioral (Morris water maze, open field, zero maze, elevated plus maze assays); cognitive-associated proteins (CREB, ERK and Tau Western immunoblotting); motor coordination (Rotarod assay); structural abnormalities (immunohistological analyses), and proinflammatory cytokines (cytometric bead assay) were measured in young (2 month) and old (18 month) transgenics and compared with wild type controls. RESULTS: In old mice, male but not female transgenics exhibited a significant decrease in anxiety as compared with wild type controls, whereas female but not male transgenic mice exhibited significantly less motor coordination. No differences were observed in the Morris water maze (spatial learning). pERK levels were reduced in transgenic males but not females, while no differences were observed between genotypes for pCREB and pTau. In young mice, a modest learning and exploratory behavior was observed in transgenic mice using a limited number of mice, and at higher N values, pCREB and pERK (but not pTau) levels were reduced in transgenics. No macro- and micro-scopic structural abnormalities or proinflammatory cytokine level differences were observed. DISCUSSION: These results indicate that elevated RCAN1 isoform 4 in neurons leads to a modest cognition-related impairment that is overall stronger at 2 months, suggesting a compensatory adaptation over time. These RCAN1 isoform 4 effects may contribute to at least some of the observed phenotypes in individuals with Down syndrome and Alzheimer's.

Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration.

We previously showed a preferential degradation and down-regulation of mitochondrial DNA and RNA in hamster fibroblasts in response to hydrogen peroxide. Subsequent studies by others demonstrated that mitochondrial DNA can stimulate immune cells as a DAMP (damage associated molecular patterns) family member. However, the actual physical structure of this mitochondrial DNA DAMP and its importance in non-immune cell types are poorly understood. Here we report that transfected oxidant-initiated degraded mitochondrial polynucleotides, which we term "DeMPs", strongly induce the proinflammatory cytokines interleukin 6, monocyte chemotactic protein-1, and tumor necrosis factor α in mouse primary astrocytes. Additionally, proinflammatory IL1ß was induced, implicating DeMPs in inflammasome activation. Furthermore, human cerebrospinal fluid (CSF) and plasma were found to contain detectable DeMP signal. Finally, significant degradation of mitochondrial DNA was observed in response to either a bolus or steady state hydrogen peroxide. Combined, these studies demonstrate, all for the first time, that a pathophysiologically relevant form of mitochondrial DNA (degraded) can elicit a proinflammatory cytokine induction; that a brain cell type (astrocytes) elicits a proinflammatory cytokine induction in response to these DeMPs; that this induction includes the inflammasome; that astrocytes are capable of inflammasome activation by DeMPs; that DeMPs are detectable in CSF and plasma; and that hydrogen peroxide can stimulate an early stage cellular degradation of mitochondrial DNA. These results provide new insights and are supportive of our hypothesis that DeMPs are a newly identified trigger of neurodegenerative diseases such as Alzheimer's disease, which are known to be associated with early stage inflammation and oxidation.

Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation.

We have considered a novel "rational" gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, alpha-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement "recall" as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective.