Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58

Aims. Blood transfusion and postoperative anaemia are complications of total knee arthroplasty (TKA) that are associated with substantial healthcare costs, morbidity, and mortality. There are few data from large datasets on the risk factors for these complications. Methods. We retrospectively reviewed the records of TKA patients from a single tertiary care institution from February 2016 to December 2020. There were a total of 14,901 patients in this cohort with a mean age of 67.9 years (SD 9.2), and 5,575 patients (37.4%) were male. Outcomes included perioperative blood transfusion and postoperative anaemia, defined a priori as haemoglobin level < 10 g/dl measured on the first day postoperatively. In order to establish a preoperative haemoglobin cutoff, we investigated a preoperative haemoglobin level that would limit transfusion likelihood to ≤ 1% (13 g/dl) and postoperative anaemia likelihood to 4.1%. Risk factors were assessed through multivariable Poisson regression modelling with robust error variance. Results. In multivariable analyses, each gram of tranexamic acid reduced transfusion likelihood by 39% (adjusted risk ratio (ARR) 0.61 (95% confidence interval (CI) 0.47 to 0.78)). Risk factors associated with an increased risk of transfusion included operating time (ARR 2.07 (95% CI 1.54 to 2.77)) and drain use (ARR 1.73 (95% CI 1.34 to 2.24)). Conclusion. In this study, we found that increased tranexamic acid dosing, decreased operating time, and decreased drain use may reduce transfusions following TKA. We also established a single preoperative haemoglobin cutoff of 13 g/dl that could help minimize transfusions and reduce postoperative complete blood counts. Cite this article: Bone Joint J 2023;105-B(10):1086–1093

Aims. Transfusion after primary total hip arthroplasty (THA) has become rare, and identification of causative factors allows preventive measures. The aim of this study was to determine patient-specific factors that increase the risk of needing a blood transfusion. Methods. All patients who underwent elective THA were analyzed retrospectively in this single-centre study from 2020 to 2021. A total of 2,892 patients were included. Transfusion-related parameters were evaluated. A multiple logistic regression was performed to determine whether age, BMI, American Society of Anesthesiologists (ASA) grade, sex, or preoperative haemoglobin (Hb) could predict the need for transfusion within the examined patient population. Results. The overall transfusion rate was 1.2%. Compared to the group of patients without blood transfusion, the transfused group was on average older (aged 73.8 years (SD 9.7) vs 68.6 years (SD 10.1); p = 0.020) and was mostly female (p = 0.003), but showed no significant differences in terms of BMI (28.3 kg/m. 2. (SD 5.9) vs 28.7 kg/m. 2. (SD 5.2); p = 0.720) or ASA grade (2.2 (SD 0.5) vs 2.1 (SD 0.4); p = 0.378). The regression model identified a cutoff Hb level of < 7.6 mmol/l (< 12.2 g/dl), aged > 73 years, and a BMI of 35.4 kg/m² or higher as the three most reliable predictors associated with postoperative transfusion in THA. Conclusion. The possibility of transfusion is predictable based on preoperatively available parameters. The proposed thresholds for preoperative Hb level, age, and BMI can help identify patients and take preventive measures if necessary. Cite this article: Bone Jt Open 2024;5(7):560–564

Bone tissue engineering attempts at substituting critical size bone defects with scaffolds that can be primed with osteogenic cells, usually mesenchymal stem cells (MSC) from the bone marrow. Although overlooked, peripheral blood is a valuable source of MSC and circulating osteoprogenitors (COP), bearing a significant regenerative potential, and peripheral blood is easier to access than bone marrow. We thus studied osteodifferentiation of peripheral blood mononuclear cells (pbMNC) under different culture conditions, and how they compared to primary human osteoblasts. pbMNC were isolated from healthy adult volunteers by Ficoll density gradient centrifugation, and they were then cultured using media supplemented with 100nM Dexamethasone, 10mM sodium β-glycero phosphate and ascorbic acid (either 40mM or 0.05mM). For comparison, primary osteoblasts were isolated from the femoral heads of patients undergoing hip arthroplasty. After 4 weeks of culture, osteogenic activation was quantified with spectrometric measurement of alkalic phosphatase (ALP) and lactate dehydrogenase (LDH) levels. The extent of osteoid mineralization was measured with Alizarin red staining. We studied the effects of 1) varying cell concentration at seeding, 2) surface coating of culture wells with collagen and 3) high compared to low ascorbic acid (40mM and 0.05mM) media. Higher numbers of pbMNC (0.5–5.9 versus 0.062–0.25 million cells per well) at seeding resulted in a lower ALP/LDH-ratio (mean ± standard deviation), 0.39 ± 0.33 arbitrary units (AU) versus 1.36 ± 1.06 AU, but led to higher amount of osteoid production, 0.10 ± 0.06 versus 0.065 ± 0.02 AU, p < 0.05. Culture of pbMNC on collagen did not confer any difference in ALP/LDH-ratios, with 0.43 ± 0.3 AU for collagen-coated and 0.43 ± 0.41 AU for uncoated wells (p = 0.95), and we also observed no relevant difference in osteoid production (0.07 ± 0.01 AU for collagen-coated versus 0.1 ± 0.08 AU for uncoated wells, p = 0.28). Cultures of pbMNC on collagen in media supplemented with a higher concentration of ascorbic acid showed a 130% higher ALP/LDH-ratio when compared to cultures exposed to a lower ascorbic acid concentration (p < 0.05). Cultures with a low initial concentration of pbMNC (0.5 − 1 million cells) had no significantly different ALP/LDH-ratio when compared to primary human osteoblasts, but the cultures of pbMNC resulted in a 90% increase in osteoid mineralization when compared to primary human osteoblasts (p < 0.05). These findings indicate that progenitor cells derived from peripheral blood have a significant osteogenic potential, rendering them interesting candidates for seeding of scaffolds intended to fill critical sized bone defects. pbMNC produced almost double the amount of osteoid as primary osteoblasts. The isolation of pbMSC and COP is non-invasive and easy, and they might be seeded directly onto scaffolds without prior ex-vivo expansion, a question that we intend to pursue further

AIM. Retrospective study comparing the effectiveness of preoperative autologous blood donation versus intra-operative blood saver systems in minimizing the need for allogeneic blood transfusion in scoliosis surgery. MATERIALS – METHODS. Between 2003–2009, 37 of the patients (4–33, mean age 20y) who underwent scoliosis surgery, were divided in two groups. The first group (20 patients, mean age 18.7y) underwent autologous blood predonation, prerequisities were body weight over 50 kgr and Hgb above 11 mg/dl. The second group (17 patients, mean age 21.5y) consisted of patients who did not meet the above prerequisities and blood saver was used intra-operatively. Duration of surgery and perioperative Haemoglobulin (Hgb) levels were recorded in both groups. RESULTS. In group A an average of 4 autologous blood units per patient were predonated (3–5 units/patient) and the mean transfusion rate was 3.4 autologous blood units/patient. Only one patient was transfused with one allogeneic blood unit while of the 81 predeposited autologous blood units 15 were wasted (18.5%). In Group B intra-operative autotransfusion systems salvaged 302.9 ml/patient (150–500 ml/patient) while the mean transfusion rate was 2.1 allogeneic blood units/patient. CONCLUSIONS. The use of intra-operative autotransfusion systems seems to reduce the need for allogeneic blood transfusion when compared with preoperative autologous blood donation. However, the lower preoperative Hgb in Group B have to be taken under consideration. Further studies need to prove the effectiveness of these methods so that perioperative blood management minimizes the need for allogeneic blood transfusion in scoliosis surgery

Aims. The aim of this study was to examine perioperative blood transfusion practice, and associations with clinical outcomes, in a national cohort of hip fracture patients. Methods. A retrospective cohort study was undertaken using linked data from the Scottish Hip Fracture Audit and the Scottish National Blood Transfusion Service between May 2016 and December 2020. All patients aged ≥ 50 years admitted to a Scottish hospital with a hip fracture were included. Assessment of the factors independently associated with red blood cell transfusion (RBCT) during admission was performed, alongside determination of the association between RBCT and hip fracture outcomes. Results. A total of 23,266 individual patient records from 18 hospitals were included. The overall rate of blood transfusion during admission was 28.7% (n = 6,685). There was inter-hospital variation in transfusion rate, ranging from 16.6% to 37.4%. Independent perioperative factors significantly associated with RBCT included older age (90 to 94 years, odds ratio (OR) 3.04 (95% confidence interval (CI) 2.28 to 4.04); p < 0.001), intramedullary fixation (OR 7.15 (95% CI 6.50 to 7.86); p < 0.001), and sliding hip screw constructs (OR 2.34 (95% CI 2.19 to 2.50); p < 0.001). Blood transfusion during admission was significantly associated with higher rates of 30-day mortality (OR 1.35 (95% CI 1.19 to 1.53); p < 0.001) and 60-day mortality (OR 1.54 (95% CI 1.43 to 1.67); p < 0.001), as well as delays to postoperative mobilization, higher likelihood of not returning to their home, and longer length of stay. Conclusion. Blood transfusion after hip fracture was common, although practice varied nationally. RBCT is associated with adverse outcomes, which is most likely a reflection of perioperative anaemia, rather than any causal effect. Use of RBCT does not appear to reverse this effect, highlighting the importance of perioperative blood loss reduction. Cite this article: Bone Joint J 2022;104-B(11):1266–1272

We have investigated the effect of using tranexamic acid (TXA) during peri-acetabular osteotomy (PAO) on peri-operative blood loss and blood transfusion requirements. In addition we analysed whether the use of TXA was associated with an increased risk of venous thromboembolism (VTE) following this procedure. A consecutive series of 96 PAOs, performed by a single surgeon, were reviewed. A total of 48 patients received TXA and 48 did not. The TXA group received a continuous infusion of TXA at a rate of 10 mg/kg/h. The primary outcome measure was the requirement for blood transfusion. Secondary outcomes included total blood loss, the decrease in the level of haemoglobin in the blood, the length of hospital stay, and the complications of this treatment. The mean rate of transfusion was significantly lower in the TXA group (62.5% vs 12.5%, p < 0.001). The mean blood loss was also significantly reduced in the TXA group (1.9 L (standard deviation (. sd. ) 0.9) vs 1.5 L (. sd. 0.7), p < 0.01). No post-operative episodes of VTE were identified in either group. . The use of TXA reduced the blood loss and the rate of transfusion after PAO significantly, without adverse effects such as an increased rate of VTE. Cite this article: Bone Joint J 2015;97-B:1604–7

Aims. The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. Methods. A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. Results. The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. Conclusion. This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties. Cite this article: Bone Jt Open 2023;4(11):881–888

Aims. The aim of this study was to perform a systematic review of the evidence for the use of intraoperative cell salvage in patients undergoing revision hip arthroplasty, and specifically to analyze the available data in order to quantify any associated reduction in the use of allogenic blood transfusion, and the volume which is used. Methods. An electronic search of MEDLINE (PubMed), Embase, Scopus, and the Cochrane Library was completed from the date of their inception to 24 February 2022, using a search strategy and protocol created in conjunction with the PRISMA statement. Inclusion criteria were patients aged > 18 years who underwent revision hip arthroplasty when cell salvage was used. Studies in which pre-donated red blood cells were used were excluded. A meta-analysis was also performed using a random effects model with significance set at p = 0.05. Results. Of the 283 studies which were identified, 11 were included in the systematic review, and nine in the meta-analysis. There was a significant difference (p < 0.001) in the proportion of patients requiring allogenic transfusion between groups, with an odds ratio of 0.331 (95% confidence interval (CI) 0.165 to 0.663) associated with the use of cell salvage. For a total of 561 patients undergoing revision hip arthroplasty who were treated with cell salvage, 247 (44.0%) required allogenic transfusion compared with 418 of 643 patients (65.0%) who were treated without cell salvage. For those treated with cell salvage, the mean volume of allogenic blood which was required was 1.95 units (390 ml) per patient (0.7 to 4.5 units), compared with 3.25 units (650 ml) per patient (1.2 to 7.0 units) in those treated without cell salvage. The mean difference of -1.91 units (95% CI -4.0 to 0.2) in the meta-analysis was also significant (p = 0.003). Conclusion. We found a a significant reduction in the need for allogenic blood transfusion when cell salvage was used in patients undergoing revision hip arthroplasty, supporting its routine use in these patients. Further research is required to determine whether this effect is associated with types of revision arthroplasty of differing complexity. Cite this article: Bone Joint J 2023;105-B(10):1038–1044

The management of autologous blood aims at reducing the need for allogenic transfusion. Blood requirement (autologous and/or allogenic) will depend on the pre-operative red blood cell stock and on the perioperative blood loss. The red cell stock is related to body weight and preoperative haemoglobin (haematocrit) level; it can be calculated accurately, whereas the perioperative blood loss (external and occult) is variable and unpredictable. Preoperative donation of autologous blood, as well as intraoperative and/or postoperative recuperation and reinfusion of shed blood decrease the risk for allogenic transfusion in total hip replacement (THR) and total knee replacement (TKR) surgery. However, their efficiency and cost effectiveness are not optimal when applied to unselected patients. Up to 50% of the predonated units of autologous blood are wasted after THR and THK surgery if patients have not been specifically selected to predonate blood. In hip surgery the volume reinfused after intraoperative blood recuperation obviously depends on intraoperative bleeding; it averages 500 ml in a hip revision operation. In TKR (with a tourniquet) the volume reinfused after postoperative recuperation depends on the amount of blood drained in the immediate postoperative period, which reflects both the amount of bleeding and the efficiency of the drainage. On average, 500 ml of shed blood with a haematocrit of 35% is reinfused, which increases the haemoglobin level by 1.0 gr/dl on average. The efficiency of this technique is unpredictable, with a wide dispersion of individual values (standard deviation: 208 ml) for the volumes reinfused. However, in patients with a body weight of 70 kg or less, the increase in haemoglobin level was more predictable and averaged 1.23 gr/dl. In order to improve the efficiency of these two techniques (preoperative autologous blood donation and recuperation/reinfusion of shed blood), patients need to be targeted, taking into account:. - the calculated preoperative (day before surgery) red blood cell stock and the number of units of predonated blood,. - the lowest postoperative haemoglobin and haematocrit level clinically tolerable for that specific patient,. - the expected perioperative blood loss, which depends on such factors as duration of surgery, anticoagulant administration, use of a tourniquet,etc). As a general rule, a haemoglobin level < 13 gr/dl, age > 65 years and weight < 70 kg all increase the risk to require autologous or allogenic blood transfusion, and would justify planning predonation of blood and/or recuperation/reinfusion of shed blood

Aims. The pre-operative level of haemoglobin is the strongest predictor of the peri-operative requirement for blood transfusion after total knee arthroplasty (TKA). There are, however, no studies reporting a value that could be considered to be appropriate pre-operatively. . This study aimed to identify threshold pre-operative levels of haemoglobin that would predict the requirement for blood transfusion in patients who undergo TKA. . Patients and Methods. Analysis of receiver operator characteristic (ROC) curves of 2284 consecutive patients undergoing unilateral TKA was used to determine gender specific thresholds predicting peri-operative transfusion with the highest combined sensitivity and specificity (area under ROC curve 0.79 for males; 0.78 for females). Results. Threshold levels of 13.75 g/dl for males and 12.75 g/dl for females were identified. The rates of transfusion in males and females, respectively above these levels were 3.37% and 7.11%, while below these levels, they were 16.13% and 28.17%. Pre-operative anaemia increased the rate of transfusion by 6.38 times in males and 6.27 times in females. Blood transfusion was associated with an increased incidence of early post-operative confusion (odds ratio (OR) = 3.44), cardiac arrhythmia (OR = 5.90), urinary catheterisation (OR = 1.60), the incidence of deep infection (OR = 4.03) and mortality (OR = 2.35) one year post-operatively, and increased length of stay (eight days vs six days, p < 0.001). . Conclusion. Uncorrected low pre-operative levels of haemoglobin put patients at potentially modifiable risk and attempts should be made to correct this before TKA. Target thresholds for the levels of haemoglobin pre-operatively in males and females are proposed. Take home message: Low pre-operative haemoglobin levels put patients at unnecessary risk and should be corrected prior to surgery. Cite this article: Bone Joint J 2016;98-B:490–7

Abstract. Introduction. Multiple strategies, used either in isolation or combination, are available to reduce the need for post-operative blood transfusion in joint replacements. Amongst them, the use of tranexamic acid (TXA) has been rising and this study was conducted to compare the efficacy of topical and intravenous TXA in bilateral total knee replacement patients. Materials and methods. Randomised prospective study with 120 patients (male: female: 25:95) undergoing bilateral TKA. Patients were divided into two groups A and B after computer randomization, who received intravenous or topical (intra-articular) TXA respectively. Results. The average haemoglobin loss in intravenous group was 90.2379 g/L as compared to 39.137 g/L in topical group (p < 0.005). Moreover, there was reduction in blood loss in topical (330.1602 ml) as compared to intravenous group (764.9622 ml). The blood transfusion rate was more for the intravenous group (average 1.73 units) than for the topical group (average 0.75, unit). WOMAC score at 6 weeks in the intravenous group was 12.50, and in the topical group was 7.23 (p value < 0.001). Conclusion. Topical TXA is better than intravenous TXA for reduction of blood loss, which also reduces the need for blood transfusion in bilateral TKA patients

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l (13ppb, 221nmol/l). Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than ejection fraction at diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with documented blood cobalt ion levels above 13µg/l were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. All patients underwent electrocardiogram and echocardiogram assessment for signs of cardiomyopathy including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l (495nmol/l) compared to 0.01µg/l (0.2nmol/l) in the control group. There was no difference or correlation in ejection fraction (EF), left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt above 13µg/l. Further work is recommended to assess if these cardiac changes are present in patients with elevated blood cobalt levels below 13µg/l

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l. Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. The extent of cardiovascular injury, measured by global longitudinal strain (GLS), in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with prospectively collected blood cobalt ion levels above 13µg/l were identified and matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. Patients underwent echocardiogram assessment including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l compared to 0.01µg/l in the control group. There was no difference or correlation in EF, left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt

We undertook a prospective, randomised study in order to evaluate the efficacy of clamping the drains after intra-articular injection of saline with 1:500 000 adrenaline compared with post-operative blood salvage in reducing blood loss in 212 total knee arthroplasties. The mean post-operative drained blood volume after drain clamping was 352.1 ml compared to 662.3 ml after blood salvage (p < 0.0001). Allogenic blood transfusion was needed in one patient in the drain group and for three in the blood salvage group. Drain clamping with intra-articular injection of saline with adrenaline is more effective than post-operative autologous blood transfusion in reducing blood loss during total knee arthroplasty

Aims. To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Methods. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results. This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10. -11. ), RIC8A (FDR = 7.05 × 10. -4. ), and SOX12 (FDR = 1.43 × 10. -3. ). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion. Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246

Background and goal of study: Although a great percentage of the total postoperative bleeding corresponds to a hidden blood loss in the tissues and joint, visible blood from the drainage is considered the gold standard for monitoring blood loss after a knee arthroplasty. Only one study was not able to find a consistent relationship between the total blood loss and postoperative drained blood. The aim of our study was to assess the usefulness of a postoperative drainage as a monitor of bleeding following a knee arthroplasty. Material and methods: Fifty patients undergoing unilateral arthroplasty from March to November 2004, were prospectively followed until the fourth postoperative day. Drained red blood cells(RBC) loss was assessed by multiplying the drained blood volume by an haematocrit (Hct) of 30% from a pilot study. Total RBC loss and hidden RBC loss from each patient were calculated. Regression analysis was performed to assess the relationship between the total RBC loss and drained RBC loss. Results and discussions: The average age of the fifty ASA 2 patients was 72 +− 7 years. Nearly all the procedures were performed under intradural anaesthesia. Cemented technique and tourniquet were used in all cases. The mean total RBC loss was 615 +−197ml. The mean drained RBC loss was 206+− 113ml, and mean hidden RBC loss was 414 +−194ml. Thus the hidden loss was 67% of the total blood loss. Regression analysis shown a poor correlation coefficient between the total RBC loss and drained RBC loss (r= 0.31, p< 0.03)

Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)

Aims. While preoperative bloodwork is routinely ordered, its value in determining which patients are at risk of postoperative readmission following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is unclear. The objective of this study was to determine which routinely ordered preoperative blood markers have the strongest association with acute hospital readmission for patients undergoing elective TKA and THA. Methods. Two population-based retrospective cohorts were assembled for all adult primary elective TKA (n = 137,969) and THA (n = 78,532) patients between 2011 to 2018 across 678 North American hospitals using the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) registry. Six routinely ordered preoperative blood markers - albumin, haematocrit, platelet count, white blood cell count (WBC), estimated glomerular filtration rate (eGFR), and sodium level - were queried. The association between preoperative blood marker values and all-cause readmission within 30 days of surgery was compared using univariable analysis and multivariable logistic regression adjusted for relevant patient and treatment factors. Results. The mean TKA age was 66.6 years (SD 9.6) with 62% being females (n = 85,163/137,969), while in the THA cohort the mean age was 64.7 years (SD 11.4) with 54% being female (n = 42,637/78,532). In both cohorts, preoperative hypoalbuminemia (< 35 g/l) was associated with a 1.5- and 1.8-times increased odds of 30-day readmission following TKA and THA, respectively. In TKA patients, decreased eGFR demonstrated the strongest association with acute readmission with a standardized odds ratio of 0.75 per two standard deviations increase (p < 0.0001). Conclusion. In this population level cohort analysis of arthroplasty patients, low albumin demonstrated the strongest association with acute readmission in comparison to five other commonly ordered preoperative blood markers. Identification and optimization of preoperative hypoalbuminemia could help healthcare providers recognize and address at-risk patients undergoing TKA and THA. This is the most comprehensive and rigorous examination of the association between preoperative blood markers and readmission for TKA and THA patients to date. Cite this article: Bone Jt Open 2021;2(6):388–396

Introduction: Blood conservation has rapidly moved into political and medical agendas. The ongoing shortage of blood in blood banks and the discovery of vCJD pose a threat to UK blood supply with ever rising costs. The use of blood conservation techniques is increasingly being used in surgery to help reduce the need for homologous blood. We studied the use of Autologous blood transfusion drains (Bellovac ABT) in lower limb arthroplasty compared with standard closed suction drains. We studied 123 lower limb arthroplasty (61 TKR & 62 THR) to see if there was a significant reduction in the need for homologous blood transfusion when using re-transfusion drains and its cost effectiveness. Methods: Retrospective analysis of 123 patients undergone lower limb arthroplasty from March 2002 to Dec 2004 under one surgeon using the same technique for TKR and THR. 61 TKR (30 ABT drains v 31 standard drain) and 62 THR (30 ABT drains v 32 standard drain). Data was collected on sex, age, pre & post op Hb, volumes drained, volumes re-transfused and the number of homologous blood transfusions. Results: 30 THR with ABT drains: 14 male, 16 female, mean age 68.7, mean pre op Hb 13.67, mean post op Hb 10.55,mean volume re-transfused 324ml, mean volume drained 466ml. 7 patients(23%) required additional homologous blood transfusion. 32 THR with standard drains: 14 male, 18 female, mean age 68.4, mean pre op Hb 12.96, mean post op Hb 9.36, mean volume drained 579.5ml. 24 patients (75%) required homologous blood transfusion. 30 TKR with ABT drains: 14 male, 16 female, mean age 69.8, mean pre-op Hb13.4, mean post-op Hb 11.03, mean volume re-transfused 415ml, mean volume drained 580ml. 4 patients (13%) required additional homologous blood transfusion. 31 TKR with Standard drains: 13 male, 18 female. Mean age72.1, mean pre-op Hb13.33, mean post-op Hb10.4, mean volume drained 711.5ml. 14 patients (45%) required homologous blood transfusion. No re-transfusion complications occurred in the ABT group. 2 patients requiring homologous blood had increasing pyrexia and transfusion hence stopped. Discussion: 11 out of 60 patients (18%) using ABT drains required additional homologous blood compared with 38 out of 63 patients (60%) requiring homologous blood using standard drains. Pvalue< 0.001. We show a stastically significant reduction in the need for homologous blood transfusion using an autologous blood re-transfusion drain. One unit of blood costs approximately £120 the ABT drain less than half of this amount, there is a significant cost saving in using autologous blood re-transfusion drains. We conclude that using Autologous blood Re-transfusion drains is safe, cost effective and reduces the need for homologous blood transfusion. If drains are to be used then Re-transfusion drains should be used