Aims. The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate. Methods. A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model. Results. We found that an increase of one part per billion (ppb) in serum Co and Cr levels correlated significantly with worsening of the HHS in the following year. This significant correlation was also true for the HOOS-Pain and HOOS-quality of life sub scores. The overall ten-year survival rate in our cohort was 65% (95% confidence interval (CI) 52.5 to 77.6). Cox regression analysis showed a significant hazard ratio (HR) of 1.08 (95% CI 1.01 to 1.15; p = 0.028) for serum Co level. No significance was found with sex or inclination angle. Conclusion. This study shows that increasing serum Co and Cr levels measured in patients with an ASR-HRA are predictive for deterioration in HHS and HOOS subscales in the following year. Increasing serum Co and Cr should forewarn both surgeon and patient that there is a heightened risk of failure. Continued and regular review of patients with an ASR-HRA implant by measurement of serum Co/Cr levels and PROMs remains essential. Cite this article: Bone Joint J 2023;105-B(7):775–782

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05). The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer

Aims. This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant. Methods. A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life. Results. No differences in mean age (69 years, 40 to 86), mean age adapted Charlson Comorbidity Index (3.1 (SD 1.4)), mean BMI (29.2 kg/m. 2. (SD 5.8)), or number of other implants were observed between groups. Significant improvements in outcome scores and pain levels were achieved for all groups, and there was no difference in quality of life (12-Item Short-Form Health Survey questionnaire (SF-12)). Mean cobalt and chromium ion levels were significantly higher for the GenuX versus the BPKS hinged TKA (GenuX vs BPKS: cobalt: 16.3 vs 9.4 µg/l; chromium: 9.5 vs 5.2 µg/l). The TiN-coated implants did not appear to confer improvement in the metal ion levels. Metal ion concentrations above 7 µg/l were detected in 81%(29/36) of GenuX patients versus 41% (11/27) in the BPKS group. No GenuX patients had normal levels under 2 µg/l, versus 22% of BPKS patients. No significant reduction in outcome scores was observed regardless of the metal ion levels, whereas higher work-related activity was correlated with higher chromium concentrations. Conclusion. Hinged TKA, using MoM hinges, resulted in critically high cobalt and chromium ion concentrations. The BPKS hinged TKA showed significantly lower metal ion concentrations compared with the GenuX TKA. No benefits were observed using TiN coating. The different weightbearing mechanics might influence the wear of the component materials. Higher workloads and physical activity could influence chromium levels. Cite this article: Bone Joint J 2022;104-B(3):376–385

The recent resurgence in the use of metal-on-metal bearings has led to fresh concerns over metal wear and elevated systemic levels of metal ions. In order to establish if bearing diameter influences the release of metal ions, we compared the whole blood levels of cobalt and chromium (at one year) and the urinary cobalt and chromium output (at one to three and four to six years) following either a 50 mm or 54 mm Birmingham hip resurfacing or a 28 mm Metasul total hip replacement. The whole blood concentrations and daily output of cobalt and chromium in these time periods for both bearings were in the same range and without significant difference

Aims. Modular dual-mobility (DM) articulations are increasingly used during total hip arthroplasty (THA). However, concerns remain regarding the metal liner modularity. This study aims to correlate metal artifact reduction sequence (MARS)-MRI abnormalities with serum metal ion levels in patients with DM articulations. Methods. A total of 45 patients (50 hips) with a modular DM articulation were included with mean follow-up of 3.7 years (SD 1.2). Enrolled patients with an asymptomatic, primary THA and DM articulation with over two years’ follow-up underwent MARS-MRI. Each patient had serum cobalt, chromium, and titanium levels drawn. Patient satisfaction, Oxford Hip Score, and Forgotten Joint Score-12 (FJS-12) were collected. Each MARS-MRI was independently reviewed by fellowship-trained musculoskeletal radiologists blinded to serum ion levels. Results. Overall, two patients (4.4%) had abnormal periprosthetic fluid collections on MARS-MRI with cobalt levels > 3.0 μg/l. Four patients (8.9%) had MARS-MRI findings consistent with greater trochanteric bursitis, all with cobalt levels < 1.0 μg/l. A seventh patient had a periprosthetic fluid collection with normal ion levels. Of the 38 patients without MARS-MRI abnormalities, 37 (97.4%) had cobalt levels < 1.0 μg/l, while one (2.6%) had a cobalt level of 1.4 μg/l. One patient (2.2%) had a chromium level > 3.0 μg/l and a periprosthetic fluid collection. Of the 41 patients with titanium levels, five (12.2%) had titanium levels > 5.0 μg/l without associated MARS-MRI abnormalities. Conclusion. Periprosthetic fluid collections associated with elevated serum cobalt levels in patients with asymptomatic DM articulations occur infrequently (4.4%), but further assessment is necessary due to implant heterogeneity. Cite this article: Bone Joint J 2024;106-B(3 Supple A):89–96

Aims. To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood. Methods. Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR. Results. Of the 1,244 patients, 112 had normal renal function (eGFR > 90 ml/min/1.73 m. 2. ), 715 had mild renal insufficiency (eGFR 60 to 89), 384 had moderate renal insufficiency (eGFR 30 to 59), 27 had severe renal insufficiency (eGFR 15 to 29), and six had end-stage renal insufficiency (eGFR < 15). Median eGFR was 68 ml/min/1.73 m. 2. (interquartile range (IQR) 56 to 82), median whole blood Co was 3.3 µg/l (IQR 1.1 to 9.9), and median Cr was 2.0 µg/l (IQR 1.2 to 3.6). We did not observe an association between decreased eGFR and increased whole blood Co and Cr concentrations, but instead both increased Co and Cr were associated with higher eGFR, indicating better kidney function. Conclusion. As patients with MoM hip arthroplasties get older, the prevalence of renal insufficiency among them will increase, and orthopaedic surgeons will increasingly have to evaluate whether or not this affects patient follow-up. The USA Food and Drug Administration suggests that closer follow-up may be needed for MoM patients with renal insufficiency. We did not observe accumulation of blood Co or Cr in MoM hip arthroplasty patients with mild to severe renal insufficiency. Cite this article: Bone Joint J 2021;103-B(7):1231–1237

We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood. The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process

Aims. In metal-on-polyethylene (MoP) total hip arthroplasty (THA), large metal femoral heads have been used to increase stability and reduce the risk of dislocation. The increased size of the femoral head can, however, lead to increased taper corrosion, with the release of metal ions and adverse reactions. The aim of this study was to investigate the relationship between the size of the femoral head and the levels of metal ions in the blood in these patients. Methods. A total of 96 patients were enrolled at two centres and randomized to undergo MoP THA using either a 32 mm metal head or a femoral head of between 36 mm and 44 mm in size, being the largest possible to fit the thinnest available polyethylene insert. The levels of metal ions and patient-reported outcome measures (Oxford Hip Score, University of California, Los Angeles Activity Scale) were recorded at two and five years postoperatively. Results. At five years, the median levels of chromium, cobalt, and titanium were 0.5 μg/l (interquartile range (IQR) 0.50 to 0.62), 0.24 μg/l (IQR 0.18 to 0.30), and 1.16 μg/l (IQR 1.0 to 1.68) for the 32 mm group, and 0.5 μg/l (IQR 0.5 to 0.54), 0.23 μg/l (IQR 0.17 to 0.39), and 1.30 μg/l (IQR 1 to 2.05) for the 36 mm to 44 mm group, with no significant difference between the groups (p = 0.825, p = 1.000, p = 0.558). There were increased levels of metal ions at two years postoperatively in seven patients in the 32 mm group, compared with four in the 36 mm to 44 mm group, and at five years postoperatively in six patients in the 32 mm group, compared with seven in the 36 mm to 44 mm group. There was no significant difference in either the OHS (p = 0.665) or UCLA (p = 0.831) scores between patients with or without an increased level of metal ions. Conclusion. In patients who underwent MoP THA, we found no differences in the levels of metal ions five years postoperatively between those with a femoral head of 32 mm and those with a femoral head of between 36 mm and 44 mm, and no corrosion-related revisions. As taper corrosion can start after five years, there remains a need for longer-term studies investigating the relationship between the size of the femoral head size and corrosion in patients undergoing MoP THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):31–37

Aims. To determine whether there is any association between glomerular filtration rate (GFR) and blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasty. Patients and Methods. We identified 179 patients with a unilateral 36 mm diameter head as part of a stemmed Summit-Pinnacle MoM hip arthroplasty. GFR was calculated using the Modification of Diet in Renal Disease formula. Results. Normal renal function (GFR ≥ 90 ml/min/1.73 m. 2. ) was seen in 74 patients. Mild renal insufficiency (GFR 60 to 89 ml/min/1.73 m. 2. ) was seen in 90 patients and moderate renal insufficiency (GFR 30 to 59 ml/min/1.73 m. 2. ) in 15. There was no statistical difference in Co and Cr levels between patients with normal renal function and those with mild or moderate renal insufficiency. No correlation was seen between creatinine and blood metal ion levels or between GFR and blood metal ion levels. Linear regression analysis did not show any association between Co and Cr levels and GFR. Conclusion. We did not find any association between GFR and blood metal ion levels. Consequently, the accumulation of Co and Cr in blood due to renal insufficiency does not seem to be a major risk in patients with mild or moderate renal insufficiency. Cite this article Bone Joint J 2017;99-B:1147–52

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

We measured the levels of cobalt and chromium in the serum in three groups of patients after uncemented porous-coated arthroplasty. Group 1 consisted of 14 consecutive patients undergoing revision for aseptic loosening. Group 2 comprised 14 matched patients in whom the arthroplasty was stable and group 3 was 14 similarly matched patients with arthritis awaiting hip replacement. Specimens were analysed using atomic absorption spectrophotometry. Aseptic loosening of a component resulted in a significant elevation of serum cobalt (p < 0.05), but not of serum chromium. The relative risk of a component being loose, if the patient had a serum cobalt greater than 9.0 nmol/l, was 2.8

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8. +. lymphopenia) and 11 patients (13%) (CD3. +. lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8. +. lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets

Metallosis after shoulder replacement has not previously been described in the literature. We report a patient who developed extensive metallosis after implantation of an uncemented Nottingham shoulder replacement. He underwent a revision procedure.

Examination of the retrieved prosthesis showed that the titanium porous coating was separating from the humeral stem and becoming embedded in the ultra-high-molecular-weight polyethylene glenoid component, resulting in abrasive wear of the humeral component. There was metallosis despite exchange of the modular humeral head. Both components had to be exchanged to resolve the problem.

Aims

The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs).

Aims. We have previously demonstrated raised cobalt and chromium levels in patients with larger diameter femoral heads, following metal-on-polyethylene uncemented total hip arthroplasty. Further data have been collected, to see whether these associations have altered with time and to determine the long-term implications for these patients and our practice. Methods. Patients from our previous study who underwent Trident-Accolade primary total hip arthroplasties using a metal-on-polyethylene bearing in 2009 were reviewed. Patients were invited to have their cobalt and chromium levels retested, and were provided an Oxford Hip Score. Serum ion levels were then compared between groups (28 mm, 36 mm, and 40 mm heads) and over time. Results. Metal ion levels were repeated in 33 patients. When comparing the results of serum metal ion levels over time, regardless of head size, there was a significant increase in both cobalt and chromium levels (p < 0.001). Two patients with larger head sizes had undergone revision arthroplasty with evidence of trunnion damage at surgery. Two patients within the 40 mm subgroup had metal ion levels above the MHRA (Medicines and Healthcare Products Regulatory Agency) threshold for detailed investigation. The increase in cobalt and chromium, when comparing the 36 mm and 40 mm groups with those of the 28 mm group, was not significant (36 mm vs 28 mm; p = 0.092/p = 0.191; 40 mm vs 28 mm; p = 0.200/p = 0.091, respectively). There was no difference, between femoral head sizes, when comparing outcome as measured by the Oxford Hip Score. Conclusion. This study shows an increase in cobalt and chromium levels over time for all modular femoral head sizes in patients with metal-on-polyethylene bearings, with two patients demonstrating ion levels above the MHRA threshold for failure, and a further two patients requiring revision surgery. These results may have clinical implications regarding longer term follow-up of patients and future implant choice, particularly among younger patients. Cite this article: Bone Joint J 2020;102-B(7):832–837

Aims. Several different designs of hemiarthroplasty are used to treat intracapsular fractures of the proximal femur, with large variations in costs. No clinical benefit of modular over monoblock designs has been reported in the literature. Long-term data are lacking. The aim of this study was to report the ten-year implant survival of commonly used designs of hemiarthroplasty. Methods. Patients recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) between 1 September 1999 and 31 December 2020 who underwent hemiarthroplasty for the treatment of a hip fracture with the following implants were included: a cemented monoblock Exeter Trauma Stem (ETS), cemented Exeter V40 with a bipolar head, a monoblock Thompsons prosthesis (Cobalt/Chromium or Titanium), and an Exeter V40 with a Unitrax head. Overall and age-defined cumulative revision rates were compared over the ten years following surgery. Results. A total of 41,949 hemiarthroplasties were included. Exeter V40 with a Unitrax head was the most commonly used (n = 20,707, 49.4%). The overall rate of revision was small. A total of 28,201 patients (67.2%) were aged > 80 years. There were no significant differences in revision rates across all designs of hemiarthroplasty in patients of this age at any time. The revision rates for all designs were < 3.5%, three years postoperatively. At subsequent times the ETS and Exeter V40 with a bipolar head performed well in all age groups. The unadjusted ten-year mortality rate for the whole cohort was 82.2%. Conclusion. There was no difference in implant survival between all the designs of hemiarthroplasty in the first three years following surgery, supporting the selection of a cost-effective design of hemiarthroplasty for most patients with an intracapsular fracture of the hip, as determined by local availability and costs. Beyond this, the ETS and Exeter bipolar designs performed well in all age groups. Cite this article: Bone Joint J 2023;105-B(8):864–871

Aims. The first aim of this study was to evaluate whether preoperative renal function is associated with postoperative changes in whole blood levels of metal ions in patients who have undergone a Birmingham Hip Resurfacing (BHR) arthroplasty with a metal-on-metal bearing. The second aim was to evaluate whether exposure to increased cobalt (Co) and chromium (Cr) levels for ten years adversely affected renal function. Methods. As part of a multicentre, prospective post-approval study, whole blood samples were sent to a single specialized laboratory to determine Co and Cr levels, and the estimated glomerular filtration rate (eGFR). The study included patients with 117 unrevised unilateral BHRs. There were 36 females (31%). The mean age of the patients at the time of surgery of 51.3 years (SD 6.5), and they all had preoperative one-, four-, five-, and ten-year laboratory data. The mean follow-up was 10.1 years (SD 0.2). Results. Median Co levels at one year postoperatively increased significantly compared with the preoperative values, by a factor of 9.7, from 0.13 to 1.26 ppb (p < 0.001), and the median Cr levels increased significantly by a factor of 2.5, from 0.60 to 1.50 ppb (p < 0.001). Lower preoperative eGFRs were associated with significantly larger increases in Co at one year compared with the preoperative levels (ρ = -0.26; p = 0.005), but there was no relationship between preoperative eGFRs and changes in Cr at one year (ρ = -0.13; p = 0.153). Metal levels remained relatively constant with the passage of time, with a median ten-year value of 1.12 ppb for Co and 1.29 ppb for Cr. There was no significant relationship between the Co and Cr levels at ten-year follow-up and the change in eGFR from the preoperative level to that at ten years (ρ = -0.02; p = 0.827 for Co; ρ = -0.008; p = 0.933 for Cr). Conclusion. Although patients with lower preoperative eGFRs tended to have larger increases in Co levels at one year, increased metal levels for patients who underwent unilateral BHR did not adversely affect renal function during the first ten postoperative years. Cite this article: Bone Joint J 2024;106-B(3 Supple A):44–50

Aims. The Birmingham Hip Resurfacing (BHR) arthroplasty has been used as a surgical treatment of coxarthrosis since 1997. We present 20-year results of 234 consecutive BHRs performed in our unit. Methods. Between 1999 and 2001, there were 217 patients: 142 males (65.4%), mean age 52 years (18 to 68) who had 234 implants (17 bilateral). They had patient-reported outcome measures collected, imaging (radiograph and ultrasound), and serum metal ion assessment. Survivorship analysis was performed using Kaplan-Meier estimates. Revision for any cause was considered as an endpoint for the analysis. Results. Mean follow-up was 20.9 years (19.3 to 22.4). Registry data revealed that 19 hips (8.1%) had been revised and 26 patients (12%) had died from causes unrelated to the BHR. Among the remaining 189 hips, 61% were available for clinical follow-up at 20 years (n = 115) and 70% of patients had biochemical follow-up (n = 132). The cumulative implant survival rate at 20 years for male patients was 96.5% (95% confidence interval (CI) 93.5 to 99.6), and for female patients 87% (95% CI 79.7 to 94.9). The difference was statistically significant (p = 0.029). The mean Oxford Hip Score, Hip disability and Osteoarthritis Outcome Score, and Forgotten Joint Score were 45 (29 to 48), 89 (43 to 100), and 84 (19 to 100), respectively. The mean scores for each of the five domains of the EuroQol five-dimension three-level questionnaire were 1.2, 1.0, 1.2, 1.3, and 1.1, and mean overall score 82.6 (50 to 100). Ultrasound showed no pseudotumour. Mean cobalt and chromium levels were 32.1 nmol/l (1 to 374) and 45.5 nmol/l (9 to 408), respectively. Conclusion. This study shows that BHRs provide excellent survivorship and functional outcomes in young male patients. At 20 years, soft-tissue imaging and serum metal ion studies suggest that a metal-on-metal resurfacing implant can be well tolerated in a group of young patients. Cite this article: Bone Joint J 2023;105-B(9):946–952