The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients.

INTRODUCTION: Cobalt is a mitochondrial toxin, clinical cobaltism manifests with constitutional, neurologic, and cardiovascular symptomatology. Cobalt's severe toxidrome is known through case reports from extreme wear or corrosion of cobalt-chromium arthroplasty components. However, the spectrum and epidemiology of orthopedic-implant cobaltism and its relationship to duration and degree of cobalt exposure are not well defined. METHODS: The relationship of urine-cobalt concentration and duration of exposure to cobalt-chromium joint implants and cobaltism symptomatology were prospectively studied in 229 patients. Subjects received a Cobaltism-Symptom-Inventory-Score (CSIS) based on a protocolized interview and examination followed by a spot urine-cobalt measurement. RESULTS: 129 (56%) subjects were cobalturic (urine-cobalt ≥1.0 ppb). 122 (53%) subjects had a CSIS of >2, this status significantly associates with cobalturia. Median [IQR] urine-cobalt in the subjects with a CSIS >2 was 4.1[1.1-17.0] ppb compared to 0.5[0.5-1.4] ppb in subjects with CSIS ≤ 2. Cobalturia has a sensitivity of 0.69, a specificity of 0.77, and a positive predictive value of 0.74 for a CSIS of >2. The product of years-exposed to a cobalt-chromium implant and urine-cobalt by quartiles significantly positively associates with the Cobaltism-Symptom-Inventory-Score. CONCLUSION: A urine-cobalt of ≥1 ppb likely indicates adverse systemic exposure to orthopedic-implant generated cobalt. Cobaltism severity as quantified by the CSIS significantly correlates with the product of spot urine-cobalt concentration and years-exposed to a cobalt-chromium orthopedic-implant indicating a dose-response relationship. Medical provider and public awareness of orthopedic-implant cobaltism is vital because tens-of-millions are at-risk and early cobaltism is reversible. Further use of cobalt-chromium orthopedic-implants should be questioned given cobaltism becomes clinically apparent at a spot urine-cobalt of 1 ppb or greater. Monitoring of patients with high-risk cobalt-chromium orthopedic-implants appears to be indicated.

Corrosion of Polished Cobalt-Chrome Stems Presenting as Cobalt Encephalopathy.

Adverse reactions to metallic debris from corrosion of polished cobalt-chromium-cemented femoral stems are reported. Cobaltism (systemic cobalt poisoning) has not been reported from this phenomenon. Three patients presented to their surgeon for ongoing care 10-20 years after primary metal-on-plastic hip arthroplasty with the same polished cobalt-chromium-cemented femoral stems (Heritage, Zimmer). Urine cobalt was elevated, and the patients had symptoms consistent with cobaltism. Quantitative-F16DG-PET-CT brain imaging was performed showing generalized and focal brain hypometabolism consistent with cobalt encephalopathy. At revision, all stems were well fixed and grossly corroded. At 1 year after revision, cobalturia and cognitive symptoms were resolved or improved. Mechanically assisted crevice corrosion at the polymethylmethacrylate interface is a complication of polished cobalt-chromium-cemented stems that can result in systemic cobalt exposure and toxic encephalopathy. Our cases had only minor periprosthetic symptoms. Patients implanted with polished cobalt-chromium-cemented stems warrant monitoring with urine cobalt. Patients with cobaltemia warrant an evaluation for toxic encephalopathy.

F-18 FDG PET brain imaging in symptomatic arthroprosthetic cobaltism.

PURPOSE: Imaging studies of cobalt toxicity from cobalt-chromium alloy arthroprosthetics have focused on the local intra-articular and peri-articular presentation from failing joint replacements. Most studies investigating neurological findings have been small case series focused on the clinical findings of memory loss, diminished executive function, tremor, hearing and vision loss, depression, and emotional lability. This study utilizes software-based quantitative analysis of brain metabolism to assess the degree of hypometabolism and areas of susceptibility, determine if a pattern of involvement exists, and measure reversibility of findings after prosthetic revision to cobalt-free appliances. METHODS: Over 48 months, 247 consecutive patients presenting to an orthopedic clinic with an arthroprosthetic joint containing any cobalt-chromium part were screened with whole blood and urine cobalt levels. A clinically validated inventory of 10 symptoms was obtained. Symptomatic patients with a blood cobalt level above 0.4 mcg/L or urine cobalt greater than 1 mcg/L underwent F-18 FDG PET brain imaging. Analysis was performed with FDA-approved quantitative brain analysis software with the pons as the reference region. Control group was the normal brain atlas within the software. RESULTS: Of the 247 consecutively screened patients, 123 had blood and urine cobalt levels above the threshold. The 69 scanned patients had statistically significant regional hypometabolism and higher symptoms inventory. Fifty-seven patients were retained in the study. Distribution of hypometabolism was in descending order: temporal, frontal, Broca's areas, anterior cingulate, parietal, posterior cingulate, visual, sensorimotor, thalamic, and lastly caudate. Metal-on-metal (MoM) and metal-on-plastic (MoP) joint replacements produced similar patterns of hypometabolism. Of 15 patients with necessary revision surgery, 8 demonstrated improved metabolism when later re-scanned. CONCLUSION: All scanned patients had regions of significant hypometabolism. Neurological toxicity from elevated systemic cobalt levels following arthroprosthetic joint replacement has a pattern of regional susceptibility similar to heavy metals and solvents, differing from classical dementias and may occur at blood and urine cobalt levels as low as 0.4 mcg/L and 1 mcg/L, respectively. Presently accepted thresholds for cobalt exposure and monitoring may need revision. Quantitative F-18 FDG PET brain imaging may aid in the decision process for treatment options and timing of possible medical versus surgical intervention.

A Systematic Review of Systemic Cobaltism After Wear or Corrosion of Chrome-Cobalt Hip Implants.

OBJECTIVES: We sought to synthesize data on systemic arthroprosthetic cobaltism, a recently described syndrome that results from wear or corrosion of chrome-cobalt hip components. METHODS: We conducted a systematic literature review to identify all reported cases of systemic arthroprosthetic cobaltism. To assess the epidemiologic link between blood cobalt levels (B[Co]), we developed a symptom scoring tool that evaluated 9 different symptom categories and a category of medical utilization. RESULTS: We identified 25 patients reported between 2001 and 2014 with a substantial increase in case reports over the past 3 years. Symptoms were diverse and involved the hip (84%), cardiovascular system (60%), audiovestibular system (52%), peripheral motor-sensory system (48%), thyroid (48%), psychological functioning (32%), visual system (32%), and the hematological, oncological, or immune system (20%). The mean latency from implantation to presentation or revision was 41 months (range, 9-99 months). The mean B[Co] was 324 µg/L and 4 patients had levels less than 20 µg/L. The B[Co] but not blood chromium level was highly associated with a quantitative measure of overall symptom severity (r, 0.81; P < 0.001). Mean B[Co] and symptom scores were substantially higher in patients with revisions of failed ceramic-on-ceramic prostheses than those with primary metal-on-metal prostheses. CONCLUSIONS: Systemic arthroprosthetic cobaltism is an increasingly recognized complication of wear or corrosion of chrome-cobalt hip implants, may involve a large number of organ systems, and may occur with relatively low B[Co]. There is an urgent need to better define the overall scope of the problem and to develop screening and management strategies.

A Perspective on the Principles of Integrity in Infectious Disease Research.

The medical literature is prone to overstating results, a condition not thoroughly recognized among policymakers. This article sets forth examples of potential problems with research integrity in the infectious disease literature. We describe articles that may be spun, categories lumped together in hopes of creating a significant effect (and sometimes an insignificant one), changes in metrics, and how trials may fail because of suboptimal interventions. When examined together, the examples show that the problems are widespread and illustrate the difficulty associated with interpreting medical research. The state of the current medical literature makes it of utmost importance that all sections of the manuscript are read, including associated letters to the editors and information on ClinicalTrials.gov before authors' recommendations are accepted.

Systemic disease after hip replacement: aeromedical implications of arthroprosthetic cobaltism.

BACKGROUND: A multisystem illness recently reported in recipients of the newest generation of metal-on-metal hip prostheses has been ascribed to toxic effects of cobalt and possibly chromium. CASE REPORT: We present a case of insidiously developing neurologic illness that occurred in a physically active professional. DISCUSSION: This case illustrates the potential for a hip prosthesis to occultly impair safe functioning of aviators. Based on this case and others, we suggest modifications to aeromedical policy relating to waiver requests after hip replacement, including routine monitoring of serum cobalt and chromium levels in recipients of metal-on-metal hip prostheses. The evaluation of aviators having an elevated cobalt level is also discussed.

Rim cracking of the cross-linked longevity polyethylene acetabular liner after total hip arthroplasty.

BACKGROUND: Studies have suggested that cross-linked polyethylene bearings reduce wear rates from 40% to 100% compared with conventional polyethylene. However, the reduced mechanical properties of highly cross-linked polyethylene have the potential to be a limiting factor in device performance. We reviewed a series of retrieved acetabular liners with a fracture of the superior rim to assess the factors that played a role in their failure. METHODS: Four Longevity acetabular bearings, which had been retrieved from two patients after seven to twenty-seven months in vivo, were visually examined for clinical damage, were assessed with use of Fourier transform infrared spectroscopy to determine the level of oxidation, and were analyzed for mechanical properties and fracture surface characterization. Control data were obtained from never-implanted devices and from global reference ultrahigh molecular weight polyethylene bar stock as an industry calibration material. RESULTS: All four retrieved liners demonstrated articular surface wear modes, which in most cases were rated as moderate, and none were rated as severe. All showed cracking or rim failure of the liner at the superior aspect along the groove in the polyethylene that engages the locking ring of the shell. The retrieved liners had no measurable oxidation, and the mechanical properties were comparable with those of never-implanted material. CONCLUSIONS: There was no notable in vivo degradation of the retrieved liners. Important factors related to failure appear to be thin polyethylene at the cup rim, relatively vertical cup alignment, and the material properties of the highly cross-linked polyethylene that are decreased relative to conventional polyethylene. The critical dimension with respect to rim failure in modular liners appears to be the minimum thickness at the equatorial region.