Adverse Local Tissue Reactions are Common in Asymptomatic Individuals After Hip Resurfacing Arthroplasty: Interim Report from a Prospective Longitudinal Study.

BACKGROUND: The evaluation of the natural history prevalence of adverse local tissue reactions (ALTRs) using MRI has focused only on metal-on-metal (MoM) bearing surfaces without comparison to nonMoM bearing surfaces. QUESTIONS/PURPOSES: To determine (1) the longitudinal changes and differences in blood metal ion levels in patients with hip resurfacing arthroplasty (HRA), ceramic-on-ceramic (CoC) THA, and metal-on-polyethylene (MoP) THA compared with those undergoing ceramic-on-polyethylene (CoP) THA; (2) how the longitudinal change of synovial reaction classification in patients with HRA, CoC THA, and MoP THA compares with those undergoing CoP THA, and whether there is an association between the presence of an ALTR or metallosis on MRI with corresponding patient-reported outcomes, or the presence of capsular dehiscence; and (3) differences in blood metal ion levels between patients undergoing HRA with an ALTR or metallosis on MRI and those with HRA without these conditions. METHODS: Between March 2014 and February 2019, 22,723 patients underwent primary HRA and THA at one center. Patients received an HRA based on their desired athletic level after surgery and the presence of normal acetabular and proximal femoral bone morphology without osteopenia or osteoporosis. Two percent (342 of 22,723) of patients were contacted to participate, and 71% (243 of 342 hips in 206 patients) were enrolled for analysis at baseline. The patients underwent arthroplasty for degenerative joint disease, and 25 patients withdrew over the course of the study. We included patients who were more than 1 year postarthroplasty. All participants had an MRI examination and blood serum ion testing and completed a Hip Disability and Osteoarthritis Outcome Score survey annually for four years (baseline, year 1, year 2, year 3). Morphologic and susceptibility-reduced MR images were evaluated by a single radiologist not involved in the care of patients for the presence and classification of synovitis (Gwet AC1: 0.65 to 0.97), synovial thickness, and volume (coefficient of repeatability: 1.8 cm3). Linear mixed-effects models were used to compare the mean synovial thickness, synovial volume, and Hip Disability and Osteoarthritis Outcome Score subscales between bearing surfaces at each timepoint and within each bearing surface over time. Marginal Cox proportional hazards models were used to compare the time to and the risk of developing ALTR only, metallosis only, and ALTR or metallosis between bearing surfaces. All models were adjusted for age, sex, BMI, and length of implantation based on known confounders for hip arthroplasty. Adjustment for multiple comparisons was performed using the Dunnett-Hsu method. RESULTS: Patients with unilateral HRA had higher cobalt and chromium serum ion levels (baseline: 1.8 ± 0.8 ppb, year 1: 2.0 ± 1.5 ppb, year 2: 2.1 ± 1.2 ppb, year 3: 1.6 ± 0.7 ppb) than those with unilateral CoP bearings (baseline: 0.0 ± 0.1 ppb, year 1: 0.1 ± 0.3 ppb, year 2: 0.0 ± 0.2 ppb, year 3: 0.0 ± 0.0 ppb) at all timepoints (p < 0.001 for each time point). More patients who received an HRA developed ALTR or metallosis on MRI than did patients with CoP bearings (hazard ratio 4.8 [95% confidence interval 1.2 to 18.4]; p = 0.02). There was no association between the longitudinal change of synovial reaction to ALTR or metallosis on MRI with patient-reported outcomes. In addition, there was no association between the presence of dehiscence at baseline and the subsequent development of ALTR or metallosis, as seen on MRI. There were elevated cobalt (4.7 ± 3.5 ppb) and chromium (4.7 ± 2.6 ppb) serum levels in patients with unilateral HRA who had an ALTR or metallosis present on MRI at year 1 compared with patients without an ALTR or metallosis on MRI (cobalt: 1.8 ± 1.0 ppb, mean difference 4.7 ppb [95% CI 3.3 to 6.0]; p < 0.001; chromium: 2.3 ± 0.5 ppb, mean difference 3.6 ppb [95% CI 2.2 to 5.0]; p < 0.001) as well as for chromium at year 3 (3.9 ± 2.4 ppb versus 2.2 ± 1.1 ppb, mean difference 1.3 ppb [95% CI 0.3 to 2.4]; p = 0.01). CONCLUSION: We found a higher proportion of ALTR or metallosis on MRI in patients with HRA compared with patients with CoP, even when patient self-assessed symptomatology of those with an ALTR or metallosis on MRI was not different than the absence of these features. MRI detected ALTRs in high-function patients, emphasizing that an annual clinical assessment dependent on survey or blood ion testing alone may not detect soft tissue complications. The results of this study are in line with prior consensus recommendations of using MRI as part of a routine follow-up protocol for this patient population. LEVEL OF EVIDENCE: Level III, therapeutic study.

Unexpected varus deformity and concomitant metal ion release and MRI findings of modular-neck hip stems: descriptive RSA study in 75 hips with 8 years' follow-up.

Background and purpose - Modular-neck hip stems have been identified with corrosion-related problems from the neck-stem junction. We report an ongoing varus deformity of modular-neck hip stems with simultaneous metal ion release observed during a study comparing the migration of modular vs. standard hip stems.Patients and methods - We followed 50 patients with modular and 25 with standard neck stems using radiostereometry (RSA). At 5-year follow-up, we noted a compromised integrity of the modular stem with varus deformity in the neck-stem interface. Changes in head-tip distance as well as whole-blood ion concentration and MRI findings were analyzed. The modular stems were followed further up to 8 years.Results - The head-tip distance decreased continuously by 0.15 mm per year resulting in 1.2 (95% CI 1.0-1.4) mm at 8 years for modular stems, while for the standard stems at 5 years, the decrease was 0.09 (CI 0.0-0.2) mm or 0.02 mm/year. For the modular stems, the reduction in head-tip distance correlated to the increase in whole-blood cobalt concentration at 8 years but not to the MRI grading of tissue reactions. At 5 years, cobalt levels were 4.9 µg/L for modular stems and at 8 years 4.8 µg/L, whereas for standard stems this was 1.0 µg/L. After 8 years, 9 of 72 stems had been revised for different reasons, but only 1 with obvious adverse local tissue reaction (ALTR).Interpretation - We present a surprisingly large progressive deformation at the modular neck-stem junction, but so far without a definite clinical problem. Even the femoral head seems to show slight compression onto the taper over time. A high rate of revisions for the modular type of this stem has raised general concerns, and it has been recalled from the market.

Relationship between inorganic ion distribution, resting membrane potential, and the ΔG' of ATP hydrolysis: a new paradigm.

Cell membrane potential and inorganic ion distributions are currently viewed from a kinetic electric paradigm, which ignores thermodynamics. The resting membrane potential is viewed as a diffusion potential. The 9 major inorganic ions found in blood plasma (Ca2+, Na+, Mg2+, K+, H+, Cl-, HCO3-, H2PO4-, and HPO42-) are distributed unequally across the plasma membrane. This unequal distribution requires the energy of ATP hydrolysis through the action of the Na+-K+ ATPase. The cell resting membrane potential in each of 3 different tissues with widely different resting membrane potentials has been shown to be equal to the Nernst equilibrium potential of the most permeant inorganic ion. The energy of the measured distribution of the 9 major inorganic ions between extra- and intracellular phases was essentially equal to the independently measured energy of ATP hydrolysis, showing that the distribution of these 9 major ions was in near-equilibrium with the ΔG' of ATP. Therefore, thermodynamics does appear to play an essential role in the determination of the cell resting membrane potential and the inorganic ion distribution across the plasma membrane.-Veech, R. L., King, M. T., Pawlosky, R., Bradshaw, P. C., Curtis, W. Relationship between inorganic ion distribution, resting membrane potential, and the ΔG' of ATP hydrolysis: a new paradigm.

Acid-base effects of continuous infusion furosemide in clinically stable surgical ICU patients: an analysis based on the Stewart model.

OBJECTIVES: We sought to test the strength of correlation between predicted and observed systemic acid-base status based on the Stewart model equations during continuous infusion (CI) furosemide therapy. DESIGN, SETTING AND PARTICIPANTS: This was a prospective, single-center, observational study conducted in the Surgical ICU of a large academic medical center. Ten critically ill patients who received CI furosemide were included. MAIN OUTCOMES AND MEASURES: The primary purpose was to characterize the relationship between changes in serum electrolyte and acid-base status and the excretion of electrolytes in the urine during infusion of CI furosemide in critically ill patients. As a secondary endpoint, we sought to evaluate the predictive application of the Stewart model. Over 72-h, intake and output volumes, electrolyte content of fluids administered, plasma and urine electrolytes, urine pH, and venous blood gases were collected. Predicted and observed changes in acid-based status were compared for each day of diuretic therapy using Spearman's correlation coefficient. RESULTS: The mean (SD) strong ion difference (SID) increased from 45.2 (3.2) at baseline to 49.6 (4.0) after 72 h of continuous infusion furosemide. At Day 1, the mean SID (observed) (SD) was 47.5 (3.5) and the predicted SID was 49.5 (5.8). Day 1 observed plasma SID was positively correlated with the predicted SID (rs = 0.80, p = 0.01). By Days 2 and 3, the correlations of observed and predicted SID were no longer statistically significant. CONCLUSIONS AND RELEVANCE: Using the Stewart model, increases in SID as an indicator of metabolic alkalosis due to the chloruretic effects of furosemide were observed. Predicted and observed SID correlated well over the first 24 h of treatment.

Are Serum Metal Ion Levels a Concern at Mid-term Followup of Revision Knee Arthroplasty With a Metal-on-metal Hinge Design?

BACKGROUND: Elevated serum levels of chromium and cobalt ions in metal-on-metal (MoM) bearing surfaces is a well-known phenomenon in THA. However, few studies have addressed this issue in complex primary and revision knee arthroplasty using a MoM hinged mechanism, and no study, to our knowledge, has investigated knees with MoM hinges in patients without megaprostheses (tumor prostheses). QUESTIONS/PURPOSES: We analyzed a series of patients who received MoM hinged revision knee prostheses and asked: (1) What are the serum metal ion levels at short-term followup? (2) Is there any correlation between metal ion levels and the Knee Society Score (KSS) at this followup? METHODS: Between 2013 and 2017, we performed 198 revision knee arthroplasties, of which 32 (17.7%) were performed with a latest-generation MoM hinge knee design. In addition, three complex primary TKAs utilizing the same design were included in this study. The device features a metal-on-polyethylene bearing with a MoM hinge. During that period, our general indications for using a hinge were single-stage and two-stage revision surgeries, revisions with large bone defects, and primary TKA with > 20° mechanical malalignment or collateral ligament insufficiency. Of the 35 patients who received this device, 23 patients (65% of the overall group who received this implant; 11 males, 12 females) were available for followup at a median of 28 months (range, 13-61 months), and the remaining 12 (35%) patients were lost to followup. Our rationale for reporting before the more typical 2-year minimum was the finding of elevated serum ion levels with unclear clinical significance. Median age at the time of surgery was 68 years (range, 52-84 years). None of the patients included in the study had other implants with MoM bearings. Serum ion levels of chromium (III) and cobalt were assessed using mass spectrometry. Ion levels > 5 ppb were considered elevated. Clinical outcome was assessed using the original KSS. RESULTS: Median chromium serum level was 6.3 ppb (range, 0.6-31.9 ppb) and median cobalt serum level was 10.5 (range, 1.0-47.5 ppb). Of the 23 patients, 16 had elevated serum ion levels. There was a moderate correlation between KSS and both chromium (p = 0.029, r = 0.445) and cobalt (p = 0.012, r = 0.502) levels. CONCLUSIONS: Elevated metal ion levels and radiolucent lines are common after surgery with this MoM hinge design at short-term followup, and we believe this finding is of great concern. Although no patient has yet been revised, these patients will be closely monitored. We recommend that serum ion analysis become a routine part of followup after any hinge TKA in an attempt to better understand the potential consequences of this phenomenon. LEVEL OF EVIDENCE: Level IV, therapeutic study.

In vivo blood metal ion levels in patients after total shoulder arthroplasty.

BACKGROUND: Products from metal wear have been identified as a potential cause of adverse local tissue reactions and implant failure in total hip arthroplasty. However, the role of metal ion exposure in patients after total shoulder replacement is unclear. The objective of the present study was to determine in vivo blood metal ion levels of cobalt, chromium, and titanium in patients after anatomic total shoulder arthroplasty (TSA) or reverse TSA. METHODS: A consecutive series of patients after anatomic TSA or reverse TSA was evaluated retrospectively. After exclusion of patients with additional metal implants, 40 patients with unilateral anatomic TSA (n = 20) or reverse TSA (n = 20) were available for whole-blood metal ion analysis at a mean follow-up of 28 ± 9.6 months. Twenty-three healthy individuals without metal implants served as a control group. RESULTS: Mean cobalt ion concentrations were 0.18 µg/L (range, 0.1-0.66 µg/L), 0.15 µg/L (range, 0.03-0.48 µg/L), and 0.11 µg/L (range, 0.03-0.19 µg/L), mean chromium ion levels were 0.48 µg/L (range, 0.17-2.41 µg/L), 0.31 µg/L (range, 0.09-1.26 µg/L), and 0.14 µg/L (range, 0.04-0.99 µg/L), and mean titanium ion concentrations were 1.31 µg/L (range, 0.75-4.52 µg/L), 0.84 µg/L (range, 0.1-1.64 µg/L), and 0.62 µg/L (range, 0.32-2.14 µg/L) in the reverse TSA group, the anatomic TSA group, and the control group, respectively. CONCLUSIONS: TSA resulted in elevated metal ion levels compared with healthy controls, although overall metal ion concentrations measured in this study were relatively low. The role of local metal ion exposure in patients with total shoulder replacements should be further investigated.

Concordance between laboratories in metal ion testing in patients with metal-on-metal hip implants.

BACKGROUND: Testing of whole blood or serum metal ion levels has become an important part of assessing and monitoring the performance of metal-on-metal bearings, both in hip resurfacing arthroplasty and in total hip replacement. The aim of this study was to determine the concordance between 2 laboratories testing cobalt and chromium ion levels in patients with metal-on-metal bearings. METHODS: Serum and whole blood samples from patients who had undergone metal-on-metal resurfacing or large-diameter total hip arthroplasty were tested for cobalt and chromium ions in laboratory A (a recognized laboratory) and laboratory B (tasked with testing clinical specimens). Laboratory A performed cobalt and chromium testing on whole blood, and laboratory B performed cobalt testing on whole blood and chromium testing on serum. RESULTS: Samples from 104 patients were tested. Laboratory B reported lower whole blood cobalt levels than laboratory A. Furthermore, laboratory A reported that all patients had elevated whole blood cobalt ion levels compared to the normal reference values for the laboratory, whereas laboratory B reported that 46 patients (44.2%) had whole blood cobalt ion levels within the normal reference range for the laboratory. CONCLUSION: This comparative study highlights the importance of using a single laboratory for metal ion testing, as values generated from different laboratories may not be directly comparable. With recent literature suggesting that whole blood cobalt levels as low as 1 ppb may be a predictor of adverse reactions to metal debris, accurate clinical measurement needs to be increasingly exact.

CONTEXTE: Le dosage sanguin ou sérique d'ions métalliques est devenu une étape importante de l'évaluation et du suivi des prothèses à couple de frottement métal-métal utilisées en arthroplastie de resurfaçage ou totale de la hanche. La présente étude visait à évaluer la concordance entre les résultats de 2 laboratoires pour le dosage du cobalt et du chrome chez des patients porteurs de ces prothèses. MÉTHODES: Des prélèvements de sérum et de sang entier de patients porteurs d'une prothèse de resurfaçage ou d'une prothèse totale à grand diamètre de hanche à couple métal-métal ont été expédiés au laboratoire A (un laboratoire reconnu) et au laboratoire B (spécialisé en analyse d'échantillons cliniques) pour le dosage des ions cobalt et chrome. Le laboratoire A a effectué toutes ses analyses sur des prélèvements de sang entier, et le laboratoire B a utilisé le sang entier pour le dosage du cobalt et le sérum pour le dosage du chrome. RÉSULTATS: Les prélèvements de 104 patients ont été analysés. Le laboratoire B a détecté des taux sanguins de cobalt inférieurs à ceux du laboratoire A. De plus, le laboratoire A a indiqué que tous les patients présentaient des taux de cobalt sanguins élevés par rapport à ses valeurs de référence, alors que le laboratoire B a déterminé que le taux de cobalt sanguin de 46 patients (44,2 %) se trouvait dans sa fourchette de valeurs de référence normales. CONCLUSION: Cette étude comparative vient souligner l'importance de choisir un seul laboratoire pour le dosage des ions métalliques, car les valeurs générées par des établissements différents pourraient ne pas être directement comparables. Comme des études récentes semblent indiquer que des taux de cobalt sanguins aussi faibles que 1 p. p. milliard pourraient être des prédicteurs de réaction indésirable aux débris métalliques, la précision et l'exactitude des mesures cliniques revêtent une importance croissante.

Revision of ASR hip arthroplasty: analysis of two hundred and ninety six recalled patients at seven years.

PURPOSE: The aim of this study is to present an algorithm for the evaluation of both symptomatic and asymptomatic patients. METHODS: From November 2004 to May 2010, there were performed 296 operations: 245 total hip arthroplasty and 51 resurfacing arthroplasty with the ASR DePuy system. In April 2010, there was the first Medical Device Alert regarding all MoM hip replacements in the UK and in August 2010, DePuy recall started worldwide. In March 2012, we started our recall. All patients were invited to undergo clinical investigation, X-ray evaluations, and blood chrome and cobalt level determination. For a short period of time, there were performed second level exams and subsequently, we carried out MARS MRI hip study to all symptomatic patients and there was evidence of ALVAL lesions. RESULTS: To the patients with ALVAL lesions were proposed surgical hip revision while the others frequent follow-up controls. One hundred patients underwent hip surgical revision. CONCLUSIONS: We recommend constant MoM THA patients monitoring and early revision if necessary.

Has the threshold for revision surgery for adverse reactions to metal debris changed in metal-on-metal hip arthroplasty patients? A cohort study of 239 patients using an adapted risk-stratification algorithm.

Background and purpose - A risk-stratification algorithm for metal-on-metal hip arthroplasty (MoMHA) patients was devised by US experts to help clinicians make management decisions. However, the proposed algorithm did not cover all potential patient or surgical abnormalities. Therefore we adapted the US risk-stratification algorithm in MoMHA patients revised for adverse reactions to metal debris (ARMD) to determine the variability in the revision threshold, and also whether high-risk patients had inferior outcomes following revision.Patients and methods - We analysed 239 MoMHA revisions for ARMD between 2001 and 2016 from 2 centres with pre-revision blood metal ions and imaging. Patients were stratified (low risk, moderate risk, high risk) using pre-revision factors (implant, radiographic, blood metal ions, cross-sectional imaging) by adapting a published algorithm. The risk categories for each factor were assessed against revision year, revision centre, and post-revision outcomes (re-revision surgery, and any poor outcome).Results - Compared with hips revised before 2012, hips revised from 2012 onwards included more high-risk implants (44% vs. 17% pre-2012), high-risk radiographic features (85% vs. 69% pre-2012), and low-risk metal ions (41% vs. 19% pre-2012). 1 centre more frequently revised patients with high-risk implants (48% vs. 14%) and low-risk blood metal ions (45% vs. 15%) compared with the other. All these comparisons were statistically significant (p < 0.05). With the limited sample size available, implant, radiographic, blood metal ion, and cross-sectional imaging risk groups did not statistically significantly affect the rates of re-revision surgery or frequency of poor outcomes post-revision.Interpretation - When applying the adapted risk-stratification algorithm the threshold for ARMD revision changed over time, presumably due to increasing evidence, patient surveillance, and investigation since 2012. Lower blood metal ion thresholds were used from 2012 for ARMD revisions; however, there was evidence that centres attached different importance to metal ions when managing patients. High-risk patients did not have inferior outcomes following ARMD revision.

Does silvering or 11-ketotestosterone affect osmoregulatory ability in the New Zealand short-finned eel (Anguilla australis)?

Silvering has been associated with advancing osmoregulatory ability. Given the demonstrated role of 11-ketotestosterone (11KT) in mediating many of the silvering-related changes, we investigated the role of 11KT in driving this advanced osmoregulatory ability in the New Zealand short-finned eel (Anguilla australis). Yellow (non-migratory) eels with or without 11KT implants and blank-implanted silver (migratory) eels, either held in freshwater or subjected to seawater challenge, were sampled to determine serum [Na+] and [Cl-], pituitary prolactin mRNA levels, gill Na+/K+-ATPase activity and gill mRNA levels for Na+/K+-ATPase-α1 subunit and for Na+/K+/2Cl- co-transporter-1α-subunit. Developmental stage and 11KT treatment advanced the eels' osmoregulatory ability. Thus, serum [Na+] and [Cl-] were affected by developmental stage and 11KT treatment upon seawater challenge. However, seawater challenge, not 11KT treatment or developmental stage, produced the strongest and the most consistent effects on A. australis osmoregulatory processes, inducing significant effects in all the relevant parameters we measured. In light of our results and in view of the eel's marine ancestry, we contend that A. australis, or freshwater eels in general, are highly tolerant and able to adapt quickly to changing salinities even at the yellow stage, which may preclude a critical need for an advanced osmoregulatory ability at silvering.

QSAR Development for Plasma Protein Binding: Influence of the Ionization State.

PURPOSE: This study explored several strategies to improve the performance of literature QSAR models for plasma protein binding (PPB), such as a suitable endpoint transformation, a correct representation of chemicals, more consistency in the dataset, and a reliable definition of the applicability domain. METHODS: We retrieved human fraction unbound (Fu) data for 670 compounds from the literature and carefully checked them for consistency. Descriptors were calculated taking account of the ionization state of molecules at physiological pH (7.4), in order to better estimate the affinity of molecules to blood proteins. We used different algorithms and chemical descriptors to explore the most suitable strategy for modeling the endpoint. SMILES (simplified molecular input line entry system)-based string descriptors were also tested with the CORAL software (CORelation And Logic). We did an outlier analysis to establish the models to use (or not to use) in case of well recognized families. RESULTS: Internal validation of the selected models returned Q2 values close to 0.60. External validation also gave r2 values always greater than 0.60. The CORAL descriptor based model for √fu was the best, with r2 0.74 in external validation. CONCLUSIONS: Performance in prediction confirmed the robustness of all the derived models and their suitability for real-life purposes, i.e. screening chemicals for their ADMET profiling. Optimization of descriptors can be useful in order to obtain the correct results with a ionized molecule.

Correlation between Na/K ratio and electron densities in blood samples of breast cancer patients.

The main purpose of this study was to investigate the relationship between the electron densities and Na/K ratio which has important role in breast cancer disease. Determinations of sodium and potassium concentrations in blood samples performed with inductive coupled plasma-atomic emission spectrometry. Electron density values of blood samples were determined via ZXCOM. Statistical analyses were performed for electron densities and Na/K ratio including Kolmogorov-Smirnov normality tests, Spearman's rank correlation test and Mann-Whitney U test. It was found that the electron densities significantly differ between control and breast cancer groups. In addition, statistically significant positive correlation was found between the electron density and Na/K ratios in breast cancer group.

Increased Serum Ion Levels After Ceramic-on-Metal Bearing Total Hip Arthroplasty: Influence of an Asian Lifestyle.

BACKGROUND: Recent clinical studies have suggested that systemic metal ion levels are significantly elevated at midterm follow-up in patients with ceramic-on-metal (COM) bearing. However, it is not clear whether there is a correlation between patient-related factors including the lifestyle and elevated levels of serum metal ions following COM total hip arthroplasty (THA). METHODS: Serum metal levels were measured in 201 patients (234 hips) including 121 COM patients (140 hips) and 80 non-COM patients (94 hips). The Harris Hip Score, University of California, Los Angeles activity scale score, and Western Ontario and McMaster Universities Osteoarthritis Index score were measured and radiographs were obtained for the analysis. RESULTS: Significantly higher levels of cobalt (Co) and chromium (Cr) were detected in the serum of the COM THA group (Co: 1.86 ± 4.0 µg/L; Cr: 1.81 ± 2.87 µg/L) than those of the non-COM THA group (Co: 0.27 ± 0.14 µg/L; Cr: 0.19 ± 0.25 µg/L; P < .001). The serum metal levels of patients who achieved the squatting position and the kneeling position were significantly higher than those of patients who could not squat (Co: P = .033; Cr: P = .074) and kneel (Co: P = .049; Cr: P = .031). The metal ion levels of the COM THA group correlated with the total range of motion (Co: P = .0293; Cr: P = .0399). CONCLUSION: Patients who underwent a 36-mm COM THA showed high serum metal levels although good clinical outcomes at the midterm follow-up. We found that COM THA patients who were capable of greater range of motion, squatting, and kneeling are at risk of metal ion-related problems.

Inferior Radiographic and Functional Outcomes With Modular Stem in Metal-on-Metal Total Hip Arthroplasty.

BACKGROUND: Data on the association between stem type and metal-on-metal (MoM) total hip arthroplasty (THA) performance are limited. The aim of this study is to investigate the effect of stem type on the prevalence of osteolysis and radiolucency, blood metal ion levels, and functional outcomes in patients with Articular Surface Replacement THA (ASR XL), a type of MoM THA. METHODS: We analyzed 539 unilateral MoM THAs coupled with Summit (48%), Corail (35%), or S-ROM (17%) hip stems at a mean follow-up of 6.4 years. Fifty-four percent of the patients were male, and the mean age was 60 years. We studied radiographs, patient-reported outcome measures, and ion levels. RESULTS: Patients with S-ROM hip stems were 3.8 times more likely to have osteolysis (P = .003) and 7.6 times more likely to have radiolucency (P < .001) than those treated with Summit hip stems. In addition, patients treated with S-ROM hip stems scored worse than those with Summit hip stems in 4 of the 5 patient-reported outcome measures: Harris Hip Score, Visual Analog Scale pain, University of California at Los Angeles activity, and EQ-5D index. All these differences were statistically significant and ranged from 5% to 10%, which is clinically significant. CONCLUSION: Patients with S-ROM hip stems had inferior functional and radiographic results compared to patients with Summit hip stems. Retrieval studies on large diameter head MoM THA and close follow-up of these patients with hip stems are needed to understand the mechanism causing the differences in outcomes between these stem types.

An Early Report of the Use of a Modular Dual Mobility Articulation in Revision Acetabular Reconstruction.

BACKGROUND: Instability remains one of the main problems after revision hip surgery. The aim of this study was to review the clinical, radiological, and patient-reported outcomes with the use of modular dual-mobility articulation for revision acetabular reconstruction and investigate the risk of fretting corrosion by measuring serum trace metal ion levels. METHODS: Sixty consecutive patients with a minimum of 24-month follow-up after the insertion of a modular dual-mobility (Stryker, Mahwah, NJ) cup at the time of revision hip surgery were identified. Follow-up included clinical and radiological patient review and functional outcome measures, and a subset of patients had their metal ion (cobalt and chromium) levels checked. RESULTS: At the most recent follow-up, 5 patients had died, 3 patients have been revised because of ongoing instability, and 3 patients have had revision surgery due to infection. Overall functional outcome (mean Western Ontario and McMaster Universities Osteoarthritis Indexfunction 76, University of California, Los Angeles 5.6, mean Oxford 74.7, Short Form-12 physical 41.6/mental 53.3) and overall pain relief (mean Western Ontario and McMaster Universities Osteoarthritis Index pain score 78.3) scores were good. The mean satisfaction score was 78 of 100. The median serum trace metal chromium and cobalt levels at the most recent follow-up were 0.4 µg/L (range 0.1-6.1 µg/L) and 0.42 µg/L (range 0.21-9.42 µg/L), respectively. The survival with revision as the end point was 90%. CONCLUSIONS: Dual-mobility cups with modularity represent an excellent option for the patient having revision hip surgery at high risk of instability. This series presents good patient-reported outcome measures and a low complication and revision rate.

A Fully Integrated Paper-Microfluidic Electrochemical Device for Simultaneous Analysis of Physiologic Blood Ions.

A fully integrated paper microfluidic electrochemical device equipped with three different cation permeable films is developed to determine blood ions (Cl-, Na⁺, K⁺, and Ca2+) at a time. These blood ions that are normally dissolved in the real human blood stream are essential for cell metabolisms and homeostasis in the human body. Abnormal concentration of blood ions causes many serious disorders. The optimized microfluidic device working without any external power source can directly and effectively separate human blood components, and subsequently detect a specific blood ion with minimized interference. The measured sensitivity to Cl-, K⁺, Na⁺, and Ca2+ are -47.71, 45.97, 51.06, and 19.46 in mV decade-1, respectively. Potentiometric responses of the microfluidic devices to blood serum samples are in the normal ranges of each cation, and comparable with responses from the commercial blood ion analyzer Abbott i-Stat.

Optimization of Single-Step Assay for Circulating Nitrite and Nitrate Ions (NOx) as Risk Factors of Cardiovascular Mortality.

We propose an optimized single-step assay of total nitrite and nitrate concentrations based on serum deproteinization by ultrafiltration. After deproteinization, the residual protein concentration was 0.0800±0.0007 mg/ml, which secured necessary transparency of the specimens in contrast to methanol deproteinization. The optimized assay for serum nitrite and nitrate ions is characterized by high reproducibility and accuracy (variation coefficient <7%) and can be recommended for routine use in clinical practice.

Comparative Analysis of the Concentrations of Ions (Na+, K+, Ca2+, and Cl‒) in the Blood of the Brown Trout Salmo trutta from Different Rivers.

The contents of ions in the blood have been compared in three ecological groups of brown trout (parr, mature, and resident) living in rives of the basins of Lake Onega and Lake Ladoga. Brown trout from the Alats-oya (the Ladoga basin, remote from two other rivers belonging to the Onega Lake) is characterized by the lowest concentrations of the Na+, Ca2+, and Cl- ions in blood. The probable effect of the ion level in blood of brown trout on selection of life strategy is discussed.

Albumin adjustment of total calcium does not improve the estimation of calcium status.

BACKGROUND: There is a longstanding controversy as to whether plasma measurements of total calcium should be adjusted for albumin concentration, and if so which formulas are the most appropriate. METHODS: Ionised calcium, total calcium and albumin results, analysed at the same time at Uppsala University Hospital Laboratory between February 2005 and June 2013, were retrieved from a laboratory information system. The dataset included results from 20,003 patients. Total calcium was albumin-modified by a locally derived formula, based on 3106 patients from the dataset, and formulas from the literature. The agreement between the reference method ionised calcium and unadjusted total calcium and the seven different albumin-modifying calcium formulas, respectively, were compared with intra-class correlation coefficients (ICC). RESULTS: Total calcium showed substantial agreement to ionised calcium, ICC 0.85 (95% CI 0.84-0.86) for the whole validation cohort. Albumin-modified calcium by different formulas showed significantly less or equal agreement, however the locally determined formula performed better than formulas taken from the literature. Also, total calcium classified the patient as hypo-normo- or hypercalcemic right in 82% of the patients. The albumin-modified calcium did not classify patients significantly better except in the subgroup hypoalbuminemia (<30 g/L) where the local formula classified the patients slightly better than total calcium. CONCLUSIONS: Albumin modification of total calcium determinations is unlikely to add valuable information, and this practice should be abandoned. Ionised calcium should be used more frequently when aberrant results for total calcium are followed up, or in patients with known hypoalbuminemia.

Significance of the ionized calcium measurement to assess calcium status in osteopenic/osteoporosis postmenopausal outpatients.

INTRODUCTION: Evaluation of calcium status is important in the osteoporotic risk assessment. Although guidelines indicate total calcium (tCa) as first-line measurement, directly measured ionized calcium (m-iCa), considered as the gold standard, is more and more often required. Aim of this study is to evaluate the agreement between m-iCa, tCa and iCa calculated from a formula based on total calcium and albumin (c-iCa) in osteopenic/osteoporotic postmenopausal outpatients. METHODS: A total of 140 postmenopausal outpatients, 41 osteopenic (OPN) and 99 osteoporotic (OP) were enrolled. Levels of tCa, m-iCa, c-iCa, total protein and albumin, vitamin D (25-OHD), parathyroid hormone 1-84 (PTH), bone alkaline phosphatase, osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX) were also measured. RESULTS: There were no statistically significant differences between OPN and OP groups regarding values of tCa, m-iCa, and c-iCa, 25-OHD and PTH. However, OP women had lower levels of CTX (p < 0.05). A significant direct correlation between m-iCa and tCa (r = 0.60, p < 0.001) and c-iCa (r = 0.61, p < 0.001) was found. Women with isolated hyper-m-iCa had similar DEXA parameter levels respect to the other patients. However, one patient with confirmed primary hyperparathyroidism presented hyper-m-iCa versus normal tCa and c-iCa values. CONCLUSIONS: The use of tCa could be sufficient to characterize the calcium status in postmenopausal outpatients, but reflexive calcium testing strategy for m-iCa test is necessary to women presenting the low or high extremes of tCa levels, or in women with suspected PHPT.