Adverse Tissue Research Articles

The Fate of Elevated Metal Ion Levels After Revision Surgery for Head-Neck Taper Corrosion in Patients With Metal-on-Polyethylene Total Hip Arthroplasty

BackgroundElevated metal ion levels have been associated with the presence of adverse local tissue reactions in patients with metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to corrosion at head-neck taper junction. Patients are frequently concerned with their elevated systemic metal ion levels. This study investigated the rate of decline of serum cobalt and chromium ion levels after revision surgery. MethodsA total of 39 patients with MoP THA were revised because of the presence of symptomatic adverse local tissue reactions on magnetic resonance imaging with elevated serum metal ion levels. The time between initial implantation of MoP THA (index surgery) and revision surgery was considered the duration of metal exposure. The prerevision measure of ion level was considered the intensity of exposure. Prerevision median serum Co and Cr levels, as well as revision serum Co/Cr ratio, were reported. ResultsThe median serum levels of cobalt and cobalt-to-chromium ratio significantly decreased from prerevision levels of 8.2 μg/L (0.2-56.1 μg/L) and 5.6 μg/L (0.1-53.3 μg/L) to 3.1 μg/L (0.2-14 μg/L) and 1.7 μg/L (0.4-3.8 μg/L) at postrevision (P < .01), respectively. The rate of decline of Co was 0.45% per day during the first month. For chromium, the rate of decline was slower with 0.08% per day during the first month. ConclusionAt 3 months after revision surgery, cobalt and chromium ion levels declined by 34% and 8% of prerevision level, respectively. This study provides evidence-based practical information for surgeons to provide MoP THA patients when considering revision surgery for head-neck taper corrosion.

What Factors Drive Taper Corrosion?

Adverse local tissue reactions to corrosion products can lead to total hip arthroplasty failure. Although this problem has been well known for more than 25 years, it has seemingly increased in frequency over the recent years. The occurrence of corrosion is multifactorial—depending on implant, patient, and surgeon factors. As of now, there is no “one-size-fits-all” solution to prevent corrosion in total hip arthroplasty devices. Thus, it is imperative to fully understand the exact mechanisms of modular junction corrosion to prevent premature implant failure. This review highlights a few key concepts that need to be explored to minimize the impact of corrosion. The key concepts include (1) the prevention of micromotion, (2) the role of implant alloy metallurgy in the corrosion process, (3) the in vivo generation of a corrosive environment, and (4) potential unanticipated problems.

Impact of nitinol stent surface processing on in-vivo nickel release and biological response

Although nitinol is widely used in percutaneous cardiovascular interventions, a causal relationship between nickel released from implanted cardiovascular devices and adverse systemic or local biological responses has not been established. The objective of this study was to investigate the relationship between nitinol surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents manufactured using select surface treatments were implanted into the iliac arteries of minipigs for 6 months. Clinical chemistry profile, complete blood count, serum and urine nickel analyses were performed periodically during the implantation period. After explant, stented arteries were either digested and analyzed for local nickel concentration or fixed and sectioned for histopathological analysis of stenosis and inflammation within the artery. The results indicated that markers for liver and kidney function were not different than baseline values throughout 180 days of implantation regardless of surface finish. In addition, white blood cell, red blood cell, and platelet counts were similar to baseline values for all surface finishes. Systemic nickel concentrations in serum and urine were not significantly different between processing groups and comparable to baseline values during 180 days of implantation. However, stents with non-optimized surface finishing had significantly greater nickel levels in the surrounding artery compared to polished stents. These stents had increased stenosis with potential for local inflammation compared to polished stents. These findings demonstrate that proper polishing of nitinol surfaces can reduce in-vivo nickel release locally, which may aid in minimizing adverse inflammatory reactions and restenosis. Statement of significanceNitinol is a commonly used material in cardiovascular medical devices. However, relationships between nitinol surface finishing, in-vivo metal ion release, and adverse biological responses have yet to be established. We addressed this knowledge gap by implanting single and overlapped nitinol stents with different surface finishes to assess systemic impact on minipigs (i.e. serum and urine nickel levels, liver and kidney function, immune and blood count) over the 6 month implantation period. In addition, nickel levels and histopathology in stented arteries were analyzed on explant to determine relationships between surface processing and local adverse tissue reactions. The findings presented here highlight the importance of surface processing on in-vivo nickel release and subsequent impact on local biological response for nitinol implants.

Reduction of Tribocorrosion Products When Using the Platform-Switching Concept

The reduced marginal bone loss observed when using the platform-switching concept may be the result of reduced amounts of tribocorrosion products released to the peri-implant tissues. Therefore, the purpose of this study was to compare the tribocorrosion product release from various platform-matched and platform-switched implant-abutment couplings under cyclic loading. Forty-eight titanium implants were coupled with pure titanium, gold alloy, cobalt-chrome alloy, and zirconia abutments forming either platform-switched or platform-matched groups (n = 6). The specimens were subjected to cyclic occlusal forces in a wet acidic environment for 24 h followed by static aqueous immersion for 6 d. The amount of metal ions released was measured using inductively coupled plasma mass spectrometry. Microscopic evaluations were performed pre- and postimmersion under scanning electron microscope (SEM) equipped with energy-dispersive spectroscopy X-ray for corrosion assessment at the interface and wear particle characterization. All platform-switched groups showed less metal ion release compared with their platform-matched counterparts within each abutment material group (P < 0.001). Implants connected to platform-matched cobalt-chrome abutments demonstrated the highest total mean metal ion release (218 ppb), while the least total mean ion release (11 ppb) was observed in the implants connected to platform-switched titanium abutments (P ≤ 0.001). Titanium was released from all test groups, with its highest mean release (108 ppb) observed in the implants connected to platform-matched gold abutments (P < 0.001). SEM images showed surface tribocorrosion features such as pitting and bands of fretting scars. Wear particles were mostly titanium, ranging from submicron to 48 µm in length. The platform-matched groups demonstrated a higher amount of metal ion release and more surface damage. These findings highlight the positive effect of the platform-switching concept in the reduction of tribocorrosion products released from dental implants, which consequently may minimize the adverse tissue reactions that lead to peri-implant bone loss.

Revision total hip replacement using long curved fully hydroxyapatite-coated modular stems with distal interlocking

Successful femoral reconstruction in revision total hip replacement needs to address variable metadiaphyseal bone defects and still represents a controversial issue. We present our clinical experience with the use of two types of long revision, curved, fully hydroxyapatite (HA)-coated titanium femoral stems with distal interlocking. A group of 20 patients has been followed up clinically and radiographically for a period of 12.1 months (3-30 months). Indications included aseptic and septic loosening as well as adverse local tissue reactions (ALTR) to metal debris. The major complications in our series included postoperative instability and intraoperative periprosthetic femoral fracture. Revision curved modular fully HA-coated stems with distal interlocking provide for good primary stem stability and successful secondary osteointegration in revision total hip arthroplasty (THA) for both aseptic and septic loosening in the setting of femoral bone defects. Longer follow-up in a larger cohort of patients is needed to confirm the good and very good short-term results and assess femoral bone remodeling.

A Modular Polymer Platform that Delivers Recombinant Cytokines and Cisplatin Allows for De-Escalation of Radiation Therapy in an Animal Model of Head and Neck Squamous Cell Carcinoma

To evaluate the safety and efficacy of a novel modular polymer platform for head and neck squamous cell carcinoma (HNSCC). 50% of HNSCC patients fail primary management, and salvage of patients with recurrent disease is of paramount importance. We had previously shown the antitumor efficiency of this novel polymer in delivering chemokines (CCl21) and cisplatin in an animal model of SCCHN. Here we evaluate the safety and efficacy of this polymer in combination with radiation therapy (RT) in an effort to see if this combination allows for a de-escalation of RT. SCCVII/SF tumors were established in in C3H/HeJ mice. Tumors were then treated with either (1) no polymer, (2) plain polymer, (3) CCl21-polymer, (4) cisplatin polymer, and (5) combination CCl21 and cisplatin secreting polymer. The mice were then treated with three different doses of RT. Tumor size was measured every day until the mice were euthanized. Four weeks later, necropsy was performed to evaluate for vascular or nerve damage and to assess tumor size and weight. Cisplatin-polymer, CCL21-polymer, and the combination CCl21-cisplatin polymer effectively reduced SCCVII/SF tumors in the C3H/HeJ mice by over 16-fold (P<.01) as compared to control and plain polymer groups. Additionally, treatment with Cisplatin-polymer, CCL21-polymer and the combination CCl21-cisplatin polymer allowed for a 4-fold reduction in the dose of RT required. Histopathology revealed no adverse tissue effects when the cisplatin polymer was inserted in direct contact with the carotid artery, jugular vein or vagus nerve. Our promising results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC that is safe and efficacious. Our data provides a strong rationale for further evaluation of this polymer in de-intensification of radiation therapy. Once this polymer platform is further optimized we will plan for the ultimate validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.

TLR-4 expression in corrosion metal debri induced hypoxic milieu around stainless steel fracture plates

The release of corrosion debris from metallic implants leading to adverse tissue reactions and pain has jeopardized the lives of patients. This study attempts to observe if this holds true for widely used cost efficient stainless steel fracture plates and screws by studying the microenvironment in the peri prosthetic tissue of the retrieved implants. Fracture plates and nails along with adjacent tissues were collected in 10% neutral buffered formalin. Cellular response was qualitatively evaluated using HE staining and debris distribution was semi-quantitatively graded. Elemental composition of metallic debris was analysed by ESEM-EDAX of the tissue sections. The presence of macrophages, endothelial cells, TLR-4 and HIF-1α were quantitated by Immunohistochemistry and histomorphometry. Analysis of TLR-4 gene expression was carried out by real time PCR and the presence of a hypoxic milieu was confirmed by PCR Array. This study demonstrates the corrosion debris initiated chronic inflammatory reaction to stainless steel fracture plates. Nickel and Chromium ions released from implants induce a hypoxic environment resulting in TLR-4 induction. These results emphasize the need for identification of potential biomarker that could serve as a deciding factor for removal of stainless steel fracture plates from patients prior to the onset of inflammation associated reaction and also suggest the use of better manufacturing techniques and newer bio resorbable implants.

Diagnosing Taper Corrosion: When Is It the Taper and When Is It Something Else?

There has been an increasing use of modularity at the head-neck junction in total hip arthroplasty to more closely mimic the native anatomy, allowing for optimal leg length and stability. Corrosion at this junction in metal-on-polyethylene bearings can lead to an adverse local tissue reaction (ALTR). This increasingly prevalent condition should be considered in the differential diagnosis of hip pain and difficulty ambulating. A recent symposium by the American Academy of Hip and Knee Surgeons described the diagnosis, etiology, management, and prevention of taper corrosion. This article describes the history, physical, plain and advanced imaging findings, laboratory tests, and other diagnoses that should be taken into consideration when diagnosing taper corrosion. The presence of ALTR due to taper corrosion can mimic other diagnoses such as periprosthetic joint infection, instability, or aseptic loosening. Serum metal levels have been found to be the most effective screening tool for identifying corrosion, but other common causes of hip pain and difficulty ambulating should always be ruled out with the use of radiographs and common laboratory techniques before diagnosing ALTR due to corrosion.

High-frequency, low-intensity ultrasound and microbubbles enhance nerve blockade

Site 1 sodium channel blockers (S1SCBs such as tetrodotoxin [TTX] and the saxitoxins) are ultrapotent local anesthetics that bind extracellular domains of voltage-dependent sodium channels [1]. S1SCBs do not cross the blood brain barrier and have low affinity for the cardiac sodium channel isoform [2,3], and so do not cause seizures [4] or arrhythmias, making TTX an attractive alternative to conventional local anesthetics [5,6]. Local anesthesia with S1SCBs has been described in numerous reports in animal models [7–11], and is now starting to be applied in humans [12] [13]. However, due to their very hydrophilic nature S1SCBs have limited penetration to peripheral nerves even with local injection, and require relatively high concentrations to achieve consistent nerve blockade [9]. Those high concentrations can be associated with systemic toxicity. One approach to enhancing the effect of S1SCBs has been to co-inject them with second or third drugs with adjuvantic effects [7,8,14,15]. However, such couplings can entail the side-effects of the second drugs, such as the local tissue toxicity of “conventional” amino-amide and amino-ester local anesthetics or the vasoconstriction and/or tachycardia seen with epinephrine. An alternative approach is to enhance the penetration of S1SCBs to the nerve. Previously we have shown that co-injection of TTX with chemical permeation enhancers could enhance the effect of S1SCBs, albeit with some adverse tissue reaction at high concentrations [16,17]. Ultrasound-mediated drug delivery has the potential to enhance nerve blockade without adverse tissue reaction. Acoustic waves can enhance drug delivery through the sclera [18], the stratum corneum [19,20], across barriers within the gastrointestinal tract [21,22], and the blood brain barrier [23,24]. The effect of high-frequency ultrasound on drug flux across skin (sonophoresis) can be enhanced by exogenous microbubbles [25,26]. In this study, we hypothesized that ultrasound treatment would increase the flux of hydrophilic molecules, such as S1SCBs, across biological barriers to the surface of the peripheral nerve. We used TTX as a model S1SCB. We studied high-frequency, low-intensity ultrasound (HFLIU), parameters similar to those used in clinical imaging. This frequency and intensity range is theoretically safe for a broad range of applications. We evaluated the effects of HFLIU with and without the addition of exogenous microbubbles on TTX-mediated nerve blockade. We also verified whether effects of ultrasound and microbubbles were applicable to local anesthetics in general by testing their effect on the amino-amide local anesthetic bupivacaine.

Indications for MARS-MRI in Patients Treated With Metal-on-Metal Hip Resurfacing Arthroplasty

BackgroundCurrently, there are no universally accepted guidelines on when to obtain metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in metal-on-metal (MoM) hip resurfacing arthroplasty (HRA) patients. Our primary aims were to identify which patient and clinical factors are predictive of adverse local tissue reaction (ALTR) and create an algorithm for indicating MARS-MRI in patients with Articular Surface Replacement (ASR) HRA. The secondary aim was to compare our algorithm to existing guidelines on when to perform MARS-MRI in MoM HRA patients. MethodsThe study cohort consisted of 182 patients with unilateral ASR HRA from a prospective, multicenter study. Subjects received MARS-MRI at a mean of 7.8 years from surgery, regardless of symptoms. We determined which variables were predictive of ALTR and generated cutoffs for each variable. Finally, we created an algorithm to predict ALTR and indicate MARS-MRI in ASR HRA patients using these cutoffs and compared it to existing guidelines. ResultsWe found high blood cobalt (Co) (odds ratio = 1.070; P = .011) and high blood chromium (Cr) (odds ratio = 1.162; P = .002) to be significant predictors of ALTR presence. Our algorithm using a blood Co cutoff of 1.15 ppb and a Cr cutoff of 1.09 ppb achieved 96.6% sensitivity and 35.3% specificity in predicting ALTR, which outperformed the existing guidelines. ConclusionBlood Co and Cr levels are predictive of ALTR in ASR HRA patients. Our algorithm considering blood Co and Cr levels predicts ALTR in ASR HRA patients with higher sensitivity than previously established guidelines.

Potential presence of metals in patients treated with metal-metal coupling prostheses for hip arthroplasty at 7 and 10years of follow-up.

Beginning in 2008, metal-on-metal prostheses have been in the spotlight owing to much higher revision rates than expected. Adverse local tissue reactions have been well described in the literature as potential complications. Between 2012 and 2013, 13 patients with metal-on-metal total hip replacements were evaluated clinically and radiologically and with laboratory samples. The same tests were repeated between 2015 and 2016 on eight patients to assess any changes. In the laboratory assessment, we searched for chromium, cobalt, molybdenum, and nickel in blood and urine samples over 24h. Clinical assessment has shown good score in all patients except one. On a second examination, between 2015 and 2016, all patients obtained results similar to those obtained in the first assessment, except a patient, who reported a recent fall. In the radiological assessment between 2012 and 2013, results were optimal, apart from a case of aseptic mobilization. The patients reassessed 3years after the first examination showed radiological results similar to those previously obtained, apart from a patient, who showed signals of mobilization. Metal levels found in their blood decreased in most cases after 3years. Urine levels of nickel increased in five subjects, and chromium levels increased in four, but levels of cobalt and molybdenum decreased in four patients. It could be hypothesized that the decreasing trend of metal ion levels is associated with a stable wear status. On the contrary, a progressive increase in metal ion levels must be considered as early proof of implant loosening.

Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs.

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. 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. 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 μg/L, p = 0.09) and chromium concentrations (mean, 2.9 versus 4.2 μg/L, p = 0.27). The association between genotype and revision surgery secondary to ALTRs was determined with gender as a covariate. 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). 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. 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.

Five Hundred Fifty-five Retrieved Metal-on-metal Hip Replacements of a Single Design Show a Wide Range of Wear, Surface Features, and Histopathologic Reactions.

In 2010, a widely used metal-on-metal hip implant design was voluntarily recalled by the manufacturer because of higher than anticipated failure rates at 5 years. Although there was a large published range of revision rates, numerous studies had reported a higher risk of revision for excessive wear and associated adverse tissue reactions when compared with other metal-on-metal total hips. The reasons for this were suggested by some to be related to cup design features. From retrievals of ASR metal-on-metal implants and tissue samples obtained at revision surgery, we asked the following questions: (1) What were the common and uncommon surface features? (2) What were the common and uncommon linear and volumetric wear characteristics? (3) Were there common taper corrosion characteristics? (4) What aseptic lymphocytic vasculitis-associated lesion (ALVAL) features were present in the tissues? Five hundred fifty-five ASRs, including 23 resurfacings, were studied at one academic research center. Features of wear (eg, light and moderate scratching), damage (eg, deposits, gouges), and bone attachment on the porous coating were semiquantitatively ranked from 0 (none) to 3 (> 75%) based on the amount of a feature in each region of interest by the same experienced observer throughout the study. Visible features of head taper corrosion were ranked (Goldberg score) from 1 (none) to 4 (severe) by the same observer using a previously published scoring method. An experienced tribologist measured component wear depth using a coordinate measuring machine and quantified wear volume using previously validated methods. All available tissues were sampled and examined for features of ALVAL and scored from 0 to 10 by a single observer using a method they previously developed and published. A score from 0 to 4 is considered low, 5 to 8 is considered moderate, and 9 or 10 is considered high with regard to the risk of metal hypersensitivity features in the tissues. The most common bearing surface features were light and moderate scratches and removal or postremoval damage. Discoloration and deposits were commonly observed on femoral heads (55% [305 of 553]) and less commonly on cups (30% [165 of 546]). There was no evidence of impingement or dislocation damage. There was typically a small amount of bone attachment in at least one of eight designated regions of interest (84% [460 of 546]); extensive or no bone attachment was uncommon. Edge wear was highly prevalent. The maximum wear of 469 cups (88%) occurred near the edge, whereas the maximum wear of 508 femoral heads (94%) occurred between the pole and 45° from the pole. The median combined head-cup wear volume was 14 mm (range, 1-636 mm). One hundred sixty-nine pairs (32%) had a combined wear volume of < 10 mm, 42 pairs (8%) had volumetric wear of > 100 mm, and 319 pairs (60%) had wear volume between 10 and 100 mm³. Seventy-four percent of tapers (390 of 530) received a Goldberg score of 4, 22% (116 of 530) a score of 3, < 5% (24 of 530) a score of 2, and none received a score of 1. The most frequent ALVAL score was 5 out of 10 (35 of 144 hips [24%]) and ranged from 2 (one hip) to 10 (nine hips); 92 of 144 (64%) had a moderate score, 17 of 144 (12%) had a high score, and 35 (24%) had a low score. Although edge wear was prevalent, in most cases, this was not associated with high wear. The increased diameter and decreased coverage angle of the ASR design may have resulted in the observed high incidence of edge wear while perhaps decreasing the risk for impingement and dislocation. The role of bearing wear in the revisions of metal-on-metal implants is controversial, because it is known that there is a large range of in vivo wear rates even within the same implant type and that patient variability affects local tissue responses to wear debris. The observations from our study of 555 retrieved ASR implant sets indicate that there was a wide range of wear including a subset with very high wear. The results suggested that the failure of the ASR and ASR XL was multifactorial, and the failure of different subgroups such as those with low wear may be the result of mechanisms other than reaction to wear debris.

The Alpha-Defensin Test for Diagnosing Periprosthetic Joint Infection in the Setting of an Adverse Local Tissue Reaction Secondary to a Failed Metal-on-Metal Bearing or Corrosion at the Head-Neck Junction

BackgroundIn patients with adverse local tissue reaction (ALTR) secondary to a failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI. The purpose of this multicenter, retrospective study was to evaluate the accuracy of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR. MethodsWe reviewed medical records of 26 patients from 3 centers with ALTR that had an alpha-defensin test performed. Patients were assessed for PJI using the Musculoskeletal Infection Society criteria. Thirteen of these subjects had MoM total hip arthroplasty, 9 had ALTR secondary to head-neck corrosion, and 4 had MoM hip resurfacing. ResultsOnly 1 of the 26 patients met Musculoskeletal Infection Society criteria for infection. However, 9 hips were alpha-defensin positive, including 1 true positive and 8 that were falsely positive (31%). All 8 of the false positives were also Synovasure positive, although 5 of 8 had an accompanying warning stating the results may be falsely positive due to a low synovial C-reactive protein value. ConclusionSimilar to synovial fluid white blood cell count, alpha-defensin testing is prone to false-positive results in the setting of ALTR. Therefore, we recommend an aggressive approach to ruling out PJI including routine aspiration of all hips with ALTR before revision surgery to integrate the synovial fluid blood cell count, differential, cultures and adjunctive tests like alpha-defensin to allow for accurate diagnosis preoperatively.

Relationship Between 12 Adipocytokines and Distinct Components of the Metabolic Syndrome

Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it is unknown which adipocytokine or adipocytokine clusters serve as meaningful markers of metabolic syndrome (MS) components. Therefore, this study investigated the associations of 12 adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles. Twelve cytokines [adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor, chemerin, fibroblast growth factor (FGF) 19, FGF21, FGF23, insulin-like growth factor-1, interleukin 10, irisin, progranulin, and vaspin] were quantified in a cross-sectional cohort of 1046 subjects. Hypothesis-free cluster analysis, multivariate regression analyses with parameters of the MS, and discriminant analysis were performed to assess associations and the relative importance of each cytokine for reflecting MS and its components. Among the studied adipocytokines, adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS and several MS components in discriminant analyses and multiple regression models. For certain metabolic components, these adipocytokines were better discriminators than routine metabolic markers. Other cytokines investigated in the present cohort are less able to distinguish between metabolically healthy and unhealthy subjects. Adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS components in a general population, suggesting that adverse adipose tissue function is a major contributor to these metabolic abnormalities. Future prospective studies should address the question whether these adipocytokines can predict the development of metabolic disease states.

Retrieval Analysis of Large-Head Modular Metal-on-Metal Hip Replacements of a Single Design

BackgroundThere are limited publications examining modular metal-on-metal (MoM) total hip implants in which a comprehensive analysis of retrieved components is performed. This study examines 24 retrieved modular MoM implants from a single manufacturer and compares retrieval analytics; bearing surface damage, wear, and modular taper corrosion against patient, surgical and implant characteristics to elucidate significant associations. MethodsClinical, patient, and surgical data were collected including age, body mass index, blood metal ion levels, and cup inclination. Damage assessment was performed visually in addition to surface profilometry. Acetabular liners and femoral heads were measured for volumetric wear. Femoral head taper bores were similarly measured for material removal due to corrosion and fretting. ResultsPatients with MoM-related reasons for revision showed significantly higher levels of blood metal ion levels. Bearing wear was strongly associated with blood metal ion levels and was significantly increased in cups placed more vertically. Younger patients tended to have higher body mass indices as well as poorer cup placement. ConclusionThis work details a broad range of analyses on a series of modular MoM total hip implants from a single manufacturer of which there are few published studies. Acetabular cup inclination angle was deemed a primary cause of revision surgery through increased MoM wear, high metal ion levels in the blood, and subsequent adverse local tissue reactions. Heavy patients can increase the surgical difficulty which was shown to be related to poor cup placement in this cohort.

Six Degree Polished Titanium Taper &amp; CoCr Head Had No Adverse Local Tissue Reaction in Total Hip Arthroplasty: 15-year Results

Six Degree Polished Titanium Taper &amp; CoCr Head Had No Adverse Local Tissue Reaction in Total Hip Arthroplasty: 15-year Results

Adverse Wear in MOM Hip-Arthroplasty Related to the Production of Metal Fragments at Impingement Sites

Metal on metal (MOM) bearings were reintroduced as resurfacing arthroplasty (RA) for the younger, more active patient and were later incorporated into total hip arthroplasty (THA). Early results were encouraging. However, recent publications identified adverse tissue responses to metal debris, such that the majority of MOM designs have been abandoned due to the increase in cobalt-chromium (CoCr) debris and associated metal ions. Reports of MOM THA cited risks that included acetabular cups with high-inclination angles, i.e. “edge-loading”, and “trunnionosis”. Hip impingement was also a cited risk in one MOM study, with “type-IV” wear noted to be a sliding/impaction type of wear, characterized by deep scratches. Sliding/impaction wear mechanisms produced at impingement are not well represented in current MOM literature. Therefore, our objective in this review was to consolidate evidence for impingement risks. We hypothesize that hip impingement and subluxation with metal-backed acetabular cups can trigger wear mechanisms that result in, 1) femoral-neck notching, 2) release of large metal particles, 3) production of uniquely large scratches, defined as “microgrooves” on heads and cups, 4) formation of “polar” and “basal” microgrooves precisely aligning with cup profiles during impingement, and 5) equatorial microgrooves relate to soft-tissue sites of impingement. Relevant risk scenarios were evaluated and included hip impingement in both sitting and standing postures, head subluxation, wear patterns defining in-vivo component positions, and evidence for circulating metal fragments. The study relied on mapping of wear patterns to deduce in-vivo positioning of devices and relied on surrogate femoral stems of the same brand to simulate neck-cup impingement. EOS imaging techniques were used to analyze functional-sitting and functional-standing postures and prove existence of hip impingement sites in patients. The study identified 8-risk scenarios for wear damage on MOM bearings. The microgrooves on femoral-heads crossing the main-wear area (polar) and non-wear regions (basal) aligned well with cuprim profiles at impingement sites. This may represent the first description of such large scratches (40 - 300 μm wide) we termed microgrooves, that formed on femoral heads at sites representative of prosthetic impingement. As an abrasive wear process, similar to the formation of femoral-neck notches, these would have been acquired over millions of gait cycles. The pitting and linear microgrooves crossing the non-wear areas of heads (basal) represented the ingress sites of circulating metal particles. Similar micro-grooves were evident in acetabular cups, also signifying 3rd-body abrasion by large metal particles. Hip impingement and head subluxation were implicated by the unequivocal evidence of 3rd-body abrasive wear as the triggering events producing large metal fragments. One caveat regarding retrieval studies is that such damage may be only representative of failed MOM devices. This study demonstrated that emerging technologies such as EOSTM x-ray analyses can reveal subtle changes in implant positioning using patient shifts in functional postures (sitting, standing, hyper-extension, etc.), and thereby assess impingement/subluxation risks in the clinical setting before failure occurs.

The N-terminal-truncated recombinant fibrin(ogen)olytic serine protease improves its functional property, demonstrates in vivo anticoagulant and plasma defibrinogenation activity as well as pre-clinical safety in rodent model

An N-terminal truncated fibrino(geno)lytic serine protease gene encoding a ~42kDa protein from Bacillus cereus strain AB01 was produced by error prone PCR, cloned into pET19b vector, and expressed in E5 coli BL21 DE3 cells. The deletion of 24 amino acid residues from N-terminal of wild-type Bacifrinase improves the catalytic activity of [Bacifrinase (ΔN24)]. The anticoagulant potency of [Bacifrinase (ΔN24)] was comparable to Nattokinase and Warfarin and results showed that its anticoagulant action is contributed by progressive defibrinogenation and antiplatelet activities. Nonetheless, at the tested concentration of 2.0μM [Bacifrinase (ΔN24)] did not show in vitro cytotoxicity or chromosomal aberrations on human embryonic kidney cells-293 (HEK-293) and human peripheral blood lymphocytes (HPBL) cells. [Bacifrinase (ΔN24)], at a dose of 2mg/kg, did not show toxicity, adverse pharmacological effects, tissue necrosis or hemorrhagic effect after 72h of its administration in Swiss albino mice. However, at the tested doses of 0.125 to 0.5mg/kg, it demonstrated significant in anticoagulant effect as well as defibrinogenation after 6h of administration in mice. We propose that [Bacifrinase (ΔN24)] may serve as prototype for the development of potent drug to prevent hyperfibrinogenemia related disorders.

Reducing fretting-initiated crevice corrosion in hip simulator tests using a zirconia-toughened alumina femoral head.

Taper fretting corrosion is considered a potentially limiting factor for total hip arthroplasty longevity. Recently, attention has been focused on new materials for ceramic femoral heads, for example, zirconia-toughened alumina (ZTA), since they have an alternative bearing surface that can improve the wear resistance. Moreover, ceramics have high chemical stability and corrosion resistance. In this study, we evaluated the effects of ZTA and Co-Cr-Mo alloy femoral heads on their taper fretting and/or corrosion characteristics under a controlled hip simulator test. After the test, less fretting and corrosion were observed in the taper surface of the trunnion against the ZTA femoral head than for that against the Co-Cr-Mo alloy femoral head. In addition, corrosion damages were only observed in the lateral-distal taper surface (noncontact area) of the trunnion in the Co-Cr-Mo alloy femoral head group. The ZTA femoral head group also eliminated the potential for Co ion release into the lubricants from taper corrosion, reducing the possibility of adverse local tissue inflammatory responses. In conclusion, ZTA femoral heads showed markedly less fretting corrosion compared to Co-Cr-Mo alloy femoral heads and have a lower potential for metal ion release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2815-2826, 2018.