Aim. The diagnosis of septic arthritis mostly relies on clinical examination, several blood parameters including white blood cell count, C-reactive protein, sedimentation, and the analysis of the joint aspiration. However, the diagnosis can be difficult when the symptoms are vague and the information obtained from laboratory might be insufficient for definitive diagnosis. This study aimed to evaluate several ratios obtained from routine blood tests for a possible use in the diagnosis of septic arthritis. Method. The adult patients who were operated in our clinic due to septic arthritis between 2014–2020 were identified and retrospectively evaluated. The patients with any blood disorders or missing file information were excluded. A total of 36 patients were found to be eligible for inclusion. The control group included 40 patients without any sign of infection who underwent total knee arthroplasty due to knee osteoarthritis. Preoperative blood tests of each patients were examined. In addition to CRP and sedimentation values, neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet count-mean platelet volume were calculated and receiving operating characteristics (ROC) curve analysis was made to determine the sensitivity, specificity and area under curve (AUC) values of these parameters. Results. The distribution of affected joint in septic arthritis group was as follow; 22 knees, 6 hips, 4 shoulders, 2 elbows, 1 wrist and 1 ankle. The cultures of joint aspiration yielded positive result in 19 patients while the cultures were negative in 17 patients. All of the analyzed parameters were significantly different between the groups (p<0.001). ROC curve analysis results are given in detail, in Table 1 and Figure 1. The AUC value was 97.3 when only CRP and sedimentation values were used but increased to 98.6 when neutrophile/ lymphocyte ratio was added and increased to 100 when all analyzed parameters were included. Conclusions. The analyzed parameters were found to increase the overall sensitivity and specificity when used together with acute phase reactants. However, when evaluated separately, CRP and sedimentation were still found as the most valuable parameters in the diagnosis of septic arthritis. In the diagnosis of septic arthritis, 35 mm/hr cut-off value for sedimentation and 10 mg/L cut-off value for CRP were found more sensitive and specific compared to standard laboratory cut-off values of 20 mm/hr and 5 mg/L. For any tables or figures, please contact the authors directly

Aims. Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods. We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results. Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion. Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article: Bone Jt Open 2021;2(10):850–857

Background. Processing of allografts, which are used to fill bone defects in orthopaedic surgery, includes chemical cleaning as well as gamma irradiation to reduce the risk of infection. Viable bone cells are destroyed and denaturing proteins present in the graft the osteoconductive and osteoinductive characteristics of allografts are altered. The aim of the study was to investigate the mechanical differences of chemical cleaned allografts by adding blood, clotted blood, platelet concentrate and platelet gel using a uniaxial compression test. Methods. The allografts were chemically cleaned, dried and standardized according to their grain size distribution. In group BL 4 ml blood, in CB 4 ml blood and 480 μl of 1 mol calcium chloride to achieve clotting, in PC 4 ml of concentrated platelet gel, in PG 4 ml of concentrated platelets and 666 μl of 1 mol calcium chloride were added. Uniaxial compression test was carried out for the four groups before and after compating the allografts. Results. No statistically significant decrease of the initial density was observed after compaction for BL and PC. In CB a statistical significant decrease of the initial density by 10% was observed, while PG decreased its initial density after compaction by 13%. Considering the density at the yield limit before and after compaction BL showed a statistically significant decrease of 13% and PG of 14%. In CB and PC no statistically significant decrease of the density at the yield limit could be observed. All groups showed a statistical significant difference when comparing the yield limit before and after compaction. BL and PC showed a ∼35% higher yield limit after compaction, while in the groups with the activation liquid CB and PG the yield limit increased by 15% for CB and 20% for PG. No statistically significant difference between groups was found for the density at the yield limit before compaction (p=0.157), for the initial density (p=0.523), the density at the yield limit (p=0.681) and the yield limit itself (p=0.423) after compaction. A statistically significant difference between the groups under investigation was found for the initial density before compaction (p=0.041) and for the yield limit before compaction (p=0.041). BL had a statistically significant lower initial density than PG (p=0.048). All other pairwise comparisons between groups did not reach statistically significance for the initial density before compaction. Conclusion. Adding blood, PRP or PC in allografts has shown in different studies to enhance bone ingrowth. The authors recommend to chemical clean allografts for large defects, optimize their grain size distribution and add platelet concentrate or platelet rich plasma for enhancing as well primary stability as well bone ingrowth. The recommended processing procedure has to be tested in an in-vivo study

We present seven patients with recurrent haemarthroses after total knee arthroplasty, caused by an inherent platelet function defect. These patients developed painful knee swelling, persistent bleeding and/or wound breakdown, a platelet factor 3 availability defect being identified in all cases. Surgical exploration, with joint debridement, lavage and synovectomy, was performed in four patients who did not improve with conservative therapy. Histopathological examination of synovium revealed a focal synovial reaction with histiocytic infiltration, and occasional foreign-body giant cells. One patient required an early revision because of aseptic loosening of their tibial component. The condition was treated by single-donor platelet transfusions with good results. The diagnosis, management, and relevance of this disorder are discussed

The incorporation of platelet rich plasma (PRP) in the treatment of various musculoskeletal conditions has increased exponentially over the past decade. While described most often as an augment or treatment for tendinopathies and acute tendon injuries, more recently, PRP has been described as an adjunct to arthroplasty procedures, mostly with respect to knee arthroplasty. In the shoulder, only a single study has been published, in which Zavadil and colleagues performed a randomised study of 40 patients undergoing total shoulder arthroplasty undergoing either treatment with autologous platelet gel and platelet poor plasma (n=20) or undergoing no biologic treatment (control group, n=20). The authors noted that the treatment group had significantly lower pain scores, less pain medication requirements, and improved internal rotation when compared to controls; in addition, there were no significant differences in post-operative (compared to pre-operative) hemoglobin levels or length of stay. The vast majority of arthroplasty studies discussing PRP analyze the impact of treatment on wound healing, post-operative pain, post-operative range of motion, and need for post-operative blood transfusions. Unfortunately, due to the substantial variability of methodology (not all PRP preparations are the same) in the available studies as well as the variability in outcomes reporting, direct comparison between different studies is not feasible. Here, we discuss the basic science elements of PRP relevant to arthroplasty, the variability of PRP solutions, the specific applications of PRP in arthroplasty, and the latest clinical outcomes analyses of patients undergoing PRP therapy in conjunction with shoulder arthroplasty

Purpose. The recent emergence of autologous blood concentrates, such as platelet rich plasma (PRP), as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. Our objective was to determine the effectiveness of autologous blood concentrates compared with control therapy in improving pain in patients with orthopaedic bone and soft tissue injuries. Method. We conducted a systematic review of MEDLINE and EMBASE from 1996 and 1947, respectively, up to July 2010. Additional studies were identified by contacting experts, searching the bibliographies of the included studies as well as orthopaedic meeting archives. We included published and unpublished randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. Two reviewers, working in duplicate, abstracted data on study characteristics and protocol. Reviewers resolved disagreement by consensus. Results. We identified 18 randomized trials and nine prospective cohort studies. There was a lack of consistency in outcome measures across all studies. Four randomized controlled trials (N=275) and three prospective cohort studies (N=88) reported visual analog scale (VAS) scores when comparing platelet rich plasma with a control therapy across injuries to the acromion, lateral epicondyle, anterior cruciate ligament, patella, tibia and spine. There was no significant benefit for platelet rich plasma up to and including six months across randomized trial (standardized mean difference −0.35; 95% confidence interval, −0.98 to 0.28) or prospective cohort data (standardized mean difference −0.20; 95% confidence interval, −0.64 to 0.23). Conclusion. There is a lack of evidence to support the efficacy of platelet rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft tissue injuries. The literature is further complicated by a lack of standardization in study protocols, platelet separation techniques, and outcome measures

The cause of elbow tendinosis is most likely a combination of mechanical overloading and abnormal microvascular responses. Numerous methods of treatment have been advocated. In this study, we evaluated the use of platelet-rich plasma (PRP) as a treatment for resistant epicondylitis. The rationale for using platelets is that they participate predominantly in the early inflammation phases and degranulation. They constitute a reservoir of critical growth factors and cytokines which when placed directly into the damaged tissue, may govern and regulate the tissue healing process. We looked at 25 patients (19 with lateral and 6 with medial) who failed to improve after physiotherapy, cortisone injections and application of epicondylar clasps and assessed the efficacy of platelet-rich plasma injections using Gravitational platelet separation system (GPS). The cohort of patients included over a period of three years had physiotherapy, stretches, epicondylar clasp and an average of 2.9steroid injections (1–6) before having a PRP injection. The mean patient age was 43 years ranging between 24 and 54. There were 11 men and 14 women. The study included 19 patients with lateral epicondylitis and 6 patients with symptoms on the medial side. The ratio between dominant and nondominant side was according to the literature: 76%. The quick DASH scores imroved by 14% on an average in the first 3 months and further 26% in the following 9 months. 4 patients needed reintervention, 3 lateral and 1 medial and had surgical release between 6 and 12 months. 2 of them had reinjections before surgery. No local infections except mild inflammation and no systemic effects were noted. Within the limitations of being a case series and limited follow-up PRP injections provided a safe and progressive benefit over a period of 1 year in refractory cases, providing a good nonoperative alternative

Total knee arthroplasty has been associated with substantial blood loss in the perioperative period necessitating a substantial risk for blood transfusions. There are various methodologies utilized to decrease postoperative anemia and minimize the need for allogeneic blood transfusions. These include autologous pre-donation, the use of erythropoietin and the use of perioperative cell salvage. Although all of these are successful in decreasing postoperative anemia, there is still a significant risk of allogeneic blood transfusions in the postoperative period. This is a retrospective review of a consecutive series of total knee replacements investigating blood loss and the need for postoperative blood transfusions utilizing MIS surgical techniques and Symphony (tm) platelet gel as the sole means of blood conservation. PATIENT DEMOGRPAHICS. Between January 1, 2005 to December 31, 2005, 83 total knee arthroplasties were performed in a variety of community hospitals by a single orthopedic surgeon. The mean age was 64 years (SD 11.6, range 28-90) and the mean BMI was 34.1 (SD 7.6, range 21.3 to 53.4). 71% of the patients were females and 29% males. All patients, regardless of deformity, age or size, had a quad sparing MIS total knee arthroplasty performed utilizing cemented posterior stabilized components and all patellae were resurfaced. No patients pre-donated any blood products or had erythropoietin and no drains were utilized postoperatively. All patients had application of Symphony (tm) platelet gel prior to the interoperative release of the tourniquet. All patients received Coumadin on the day of surgery and were managed for four weeks postoperatively to keep their INR approximately 2.0. RESULTS. The mean preoperative hemoglobin was 14 (SD 1.2, range 10.7 to 16.6). The average postoperative hemoglobin was 10.0 (SD 1.1, range 8.0 to 14.2). The average drop in hemoglobin was 4.0 with a SD of 1.1. A total of two patients were transfused in this series of 83 patients for a total transfusion rate of 2.4%. The average length of stay was 3.4 days with the SD of 3.7. No patients suffered a CVA, myocardial infarction or pulmonary embolus in the two-month postoperative period. CONCLUSIONS. The results show that even utilizing MIS surgical techniques and Symphony (tm) platelet gel, there is still substantial blood loss in patients undergoing unilateral total knee arthroplasty utilizing cemented components with a mean drop of hemoglobin of four grams or 20% of their mean preoperative hemoglobin. However, in spite of significant loss of hemoglobin, most patients tolerated the postoperative anemia very well and there were no complications in this series related to anemia and this did not prolong their length of stay, which was an average of 3.4 days. Only a very low percentage of patient's in this series required a postoperative transfusion (2.4%). This report supports the continued use of MIS surgical techniques along with Symphony (tm) platelet gel to minimize the need for postoperative transfusions in total knee arthroplasties

Introduction. Rotator cuff tears remain a problem, with massive tears having a failure rate of repair reported of up to 60%, despite advances in surgical techniques. Tissue engineering techniques offers the possibility of regenerating damaged tendon tissue to a pre-injury state. We explore these techniques by implanting two novel tendon augmentation grafts with use of platelet rich plasma (PRP) in sheep. Methods. A total of 24 sheep were operated on, with the infraspinatus being surgically cut from its attachment to the humeral head. Each tendon was repaired using suture anchors and an interpositional implant according to 4 groups: (1) Empty control, (2) Novel collagen fibre implant with PRP (3) A novel collagen sponge implant (4) and the collagen sponge with PRP. The sheep were killed at 12 weeks and the implant site harvested and its histology evaluated. Results. Our findings showed that these novel grafts were well integrated into the tissue, with minimal inflammatory response. However, as expected, the material had not yet completely broken down. Our initial findings suggest that the combination of PRP with the collagen sponge best enhanced the repair of the tendon. Conclusion. Tissue engineered collagen graft hold great potential for the repair of tendons

Platelet Rich Plasma (PRP) has shown to be a general stimulation for repair and 1 year results showed promising success percentages. To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis with a two-year follow-up. A double-blind randomized controlled trial was conducted between May 2006 and January 2008. The trial was conducted in two Dutch teaching hospitals. 100 patients with chronic lateral epicondylitis were randomly assigned to a leucocyte-enriched PRP group (n=51) or in the corticosteroid group (n=49). Randomization and allocation to the trial group were carried out by a central computer system. Patients received either a corticosteroid injection or an autologous platelet concentrate injection through a peppering needling technique. The primary analysis included Visual Analogue Scale (VAS) pain scores and Disabilities of the Arm, Shoulder, and Hand Outcome (DASH) scores. The PRP group was more often successfully treated than the corticosteroid group (p<.0001). Success was defined as a reduction of 25% on VAS or DASH scores without a re-intervention after 2 years. When baseline VAS and DASH scores were compared with the scores at 2 years follow-up, both groups significantly improved across time (intention-to-treat principle). However, the DASH scores of the corticosteroid group returned back to baseline levels, while the PRP significantly improved (as-treated principle). There were no complications related to the use of PRP. Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and increases function significantly, exceeding the effect of corticosteroid injection even after a follow-up of two years. Future decisions for application of PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits

Purpose. Platelet-Rich Plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets and growth factors. Most published studies have investigated the effect of PRP-conditioned media on cell cultures. We are not aware of any study that has investigated whole PRP with its cellular components on human tissue cultures. This study aims to investigate the effect of PRP on cell migration from human Achilles tendon explants, and the subsequent cellular proliferative effects in culture. Methods. This is an in-vitro study on tendon explants obtained from Achilles tendon rupture patients. The samples were collected in sterile DMEM F12 solution then carefully cut into approximately 1–3mm. 3. sections. Tendon explants were cultured in three media types: 1. 100% PRP; 2. 50% PRP; and 3. 50% fetal calf serum (FCS). 1 and 2 were made up using DMEM F12 media (standard culture medium). Explants and cells were incubated at 37°c in 5% CO. 2. for 48 hours. Results. Images of the explanted tissue were taken using a Nikon TE300 microscope with Retiga CCD camera and cells around each explant were counted. Kruskal-Wallis statistical test showed that 100%PRP and 50%PRP cultured explants have significantly higher number of cells (p ≤0.002 and 0.028 respectively) when compared with 50%FCS cultured explants. Ziva ultrasensitive proliferation assay revealed that 100%PRP significantly increased cell proliferation. In addition, PicoGreen assay showed that DNA content of 100% PRP cultured cells were significantly higher than the control. The concentration of TGF-b1, VEGF, PDGF-AB and IGF-1 growth factors were significantly higher in PRP comparing to 50% FCS medium. Conclusion. Our findings show that whole PRP strongly affect the behaviour of human tenocytes, indicating that PRP may have potential role as an orthobiological agent in ruptured tendon treatments

Thrombelastography (TEG) is a point-of-care tool that can measure clot formation and breakdown using a whole blood sample. We have previously used serial TEG analysis to define hypercoagulability and increased venous thromboembolism (VTE) risk following a major fracture requiring surgical treatment. Additionally, we have used serial TEG analysis to quantify the prolonged hypercoagulable state and increased VTE risk that ensues following a hip fracture. Recently developed cartridge-based platelet mapping (PLM) using TEG analysis can be used to activate platelets at either the adenosine diphosphate (ADP) receptor or at the Thromboxane A2 (AA) receptor, in order to evaluate clot strength when platelets are activated only through those specific receptors. This study aim was to evaluate platelet contribution to hypercoagulability, in order to identify potential therapeutic targets for VTE prevention. We hypothesized that there would be a platelet-predominant contribution to hypercoagulability following a hip fracture. Patients aged 50 years or older with a hip fracture treated surgically were enrolled in this prospective cohort study. Exclusion criteria were: prior history of VTE, active malignancy, or pre-injury therapeutic dose anticoagulation. Serial TEG and PLM analyses were performed at admission, post-operative day (POD) 1, 3, 5, 7 and at 2-, 4-, 6- and 12-weeks post-operatively. All patients received thromboprophylaxis with low molecular weight heparin (LMWH) for 28 days post-operatively. Hypercoagulability was defined as maximal amplitude (MA; a measure of clot strength) over 65mm based on TEG analysis. Independent samples t-tests were used to compare MA values with this previously established threshold and a mixed effects linear regression model was used to compare MA values over time. Independent samples t-tests and Chi-sqaured analyses were used to compare between the surgical fixation and arthroplasty groups. Forty-six patients with an acute hip fracture were included, with a mean age of 77.1 (SD = 10.6) years, with 61% (N=11) being female. Twenty-six were treated with arthroplasty (56.5%), while the remainder underwent surgical fixation of their hip fractures. TEG analysis demonstrated post-operative hypercoagulability (mean MA over 65mm) at all follow-up timepoints until 12-weeks. PLM identified a platelet-mediated hypercoagulable state based on elevated ADP-MA and AA-MA, with more pronounced platelet contribution demonstrated by the AA pathway. Patients treated with arthroplasty had significantly increased AA-MA compared with ADP-MA at POD 3 and at the 12-week follow-up. Thrombelastography can be used to identify hypercoagulability and increased risk for VTE following a hip fracture. Platelet mapping analysis from this pilot study suggests a platelet-mediated hypercoagulable state that may benefit from thromboprophylaxis using an anti-platelet agent that specifically targets the AA platelet activation pathway, such as acetylsalicylic acid (ASA). This research also supports differences in hypercoagulability between patients treated with arthroplasty compared to those who undergo fracture fixation

Septic Arthritis (SA) is considered a surgical urgency/ emergency by physicians around the world. As our understanding grows, and improved diagnostic algorithms are developed, it has become apparent that competing interests in terms of accurately diagnosing concurrent osteomyelitis may supercede rapid surgical intervention when the imaging is timely. Nevertheless, even in cases of isolated SA, many patients will require repeat surgery. We aimed to assess factors which could predict this. A multicenter retrospective redcap database was created involving 20 pediatric centers from the CORTICES study group with the goal of better understanding pediatric musculoskeletal infection (PMSKI). All patients who met inclusion for the database were considered, surgeons for each site determined through imaging and chart review which patients met the diagnosis of isolated SA. Patients with concomitant abscesses or osteomyelitis were expressly excluded. Appropriate non parametric statistics were used to assess univariate significance. Multivariable logistic regression was used to assess clinical factors associated with an increased likelihood of more than one surgery. Receiver characteristics operating curve (ROC) analysis was used to determine optimal cutoffs to discriminate between children who required more than one surgery compared to those who required only one surgery. A probability algorithm was developed for the number of clinical factors present and the likelihood requiring more than one surgery following SA diagnosis. “Four hundred and fifty-four patients with isolated SA were analyzed from 20 US hospitals. Patients were 5.4 +/− 4.8 years old at admission, and the cohort was 56% male. Of the 454 patients, 47 (10.4%) needed more than one surgery. Bivariate comparisons across surgery groups found significant differences in minimum platelet count (pplatelet, a patient has a 0.3% reduction in the odds of needing more than one surgery (OR=.997; p=0.04). For each additional ten units of CRP, a patient has a 0.1% increase in the odds of needing more than one surgery (OR=1.001; p<0.001). Our predictive algorithm found that children with both risk factors had a 64% chance of requiring multiple surgeries. Higher CRP values and lower platelet values indicate more severe disease in isolated SA with a greater likelihood of repeat surgery. Higher CRP and lower platelet counts may portend multiple surgeries and caregivers of children with isolated SA should be advised as such

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Extended patient waiting lists for assessment and treatment are widely reported for planned elective joint replacement surgery. The development of regionally based Elective Orthopaedic Centres, separate from units that provide acute, urgent or trauma care has been suggested as one solution to provide protected capacity and patient pathways. These centres will adopt protocolised care to allow high volume activity and increased day-case care. We report the plan to establish a new elective orthopaedic centre serving a population of 2.4 million people. A census conducted in 2022 identified that 15000 patients were awaiting joint replacement surgery with predictions for further increases in waiting times. The principle of care will be to offer routine primary arthroplasty surgery for low risk (ASA 1 and 2) patients at a new regional centre. Pre-operative assessment and preparation will be undertaken digitally, virtually and/or in person at local centres close to the where patients live. This requires new and integrated pathways and ways of working. Predicting which patients will require perioperative transfusion of blood products is an important safety and quality consideration for new pathways. We reviewed all cases of hip and knee arthroplasty surgery conducted at our centre over a 12-month period and identified pre-operative patient related predictive factors to allow us to predict the need for the perioperative transfusion of blood products. We examined patient sex, age, pre-operative haemaglobin and platelet count, use of anti-coagulants, weight and body mass index to allow us to construct the Imperial blood transfusion tool. We have used the results of our study and the transfusion tool to propose the patient pathway for the new regional elective orthopaedic centre which we present

This study aimed to identify factors associated with increased rates of blood transfusion in patients with adolescent idiopathic scoliosis (AIS) treated with posterior spinal fusion (PSF). A retrospective case-control study was performed for AIS patients treated at a large children's hospital between August 2018 and December 2020. All patients with a diagnosis of AIS were evaluated. Data on patient demographics, AIS, and transfusion parameters were collected. Univariate regression and multivariate logistic modeling were utilized to assess risk factors associated with requiring transfusion. Odds ratios (OR) and 95% confidence interval (CI) were calculated. Surgeries were done by three surgeons and thirty anesthesiologists. To quantify the influence of anesthesia practice preferences a categorical variable was defined as “higher-transfusion practice preference”, for the provider with the highest rate of transfusion. A total of 157 AIS patients were included, of whom 56 were transfused RBC units (cases), and 101 did not receive any RBC transfusion (controls). On univariate analysis, the following variables were significantly correlated with receiving RBC transfusion: “higher-transfusion practice preference,” “administration of crystalloids,” “receiving fresh frozen plasma (FFP),” “receiving platelets,” “pre-operative hemoglobin,” “cell saver volume,” and “surgical time.” On multiple regression modeling, “pre-operative hemoglobin less than 120 g/L” (OR 14.05, 95% CI: 1.951 to 135.7) and “higher-transfusion practice preference” (OR 11.84, 95% CI: 2.505 to 63.65) were found to be meaningfully and significantly predictive of RBC transfusion. In this cohort, we identified pre-operative hemoglobin of 120 g/L as a critical threshold for requiring transfusion. In addition, we identified significant contribution from anesthesia transfusion practice preferences. Our multivariate model indicated that these two factors are the major significant contributors to allogenic blood transfusion. Although further studies are required to better understand factors contributing to transfusion in AIS patients, we suggest standardized, peri-operative evidence-based strategies to potentially help reduce variations due to individual provider preferences

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

Introduction. The ability of activated platelets to induce cellular proliferation is well recognised. In a previous diffusion model, platelets combined with Tri-calcium phosphate (TCP) led to an osteoprogenitor mitogenic response followed by cellular differentiation. This study was designed to look at osteoprogenitor responses when cultured directly onto TCP granules combined with activated platelets. Method. Human osteoprogenitors were loaded onto TCP with activated platelets at a low seeding density and high seeding densities. Cellular proliferation was assessed using the pico-green DNA content analysis. Differentiation towards osteoblastic phenotype was assessed using an alkaline phosphatase assay. RNA extraction, reverse transcription and quantitative real-time polymerase chain reaction was used to assess gene expression for type 1 collagen and osteocalcin. Histological assessment for live/dead staining and alkaline phosphatase was used on cultured granule samples. Results. In the low seeding density, platelets induced an early proliferative response compared with controls. After 14 days of culture the cells had not differentiated to an osteoblastic phenotype. When seeded at high densities, cellular differentiation was induced by the activated platelets. Significant cellular proliferation was not observed after seeding at high density. Conclusions. This study demonstrates that osteoprogenitors respond to the local environment which is modulated by both cell-cell contact factors and inflammatory cytokines from the platelets. This study helps to define the concentration of progenitors and platelets needed for further on-growth studies. It may also help define the optimal conditions for seeding cells and platelets for clinical use of composite bone graft substitutes

Rotator cuff tendon healing has proven to be a substantial clinical challenge. There is significant interest in finding biologic augmentation methods to improve this healing process. Two currently available products include platelet rich plasma/platelet rich fibrin matrix and several commercially available extra cellular matrix (ECM) patches. Platelet rich plasma is a sample of an autologous blood which has been centrifuged to a concentration of platelets three to four times that of normal. Platelets contain multiple growth factors, many of which have been shown to be involved in all phases in tendon healing. An alternative is platelet rich fibrin matrix. This forms a fibrin matrix with the platelets embedded within. Growth factors are subsequently released as the fibrin is reabsorbed. There are only a few studies which look at the effectiveness of platelet rich plasma and fibrin matrix. Overall, there is no strong evidence to support its routine use in the setting of rotator cuff repair. Extra cellular matrix patches are used to reinforce the strength of the repair and offload the tendon. They also provide the potential to form a scaffold for new growth and differentiation and may at some point be a delivery vehicle for cells and growth factors. There are currently two prospective randomised studies evaluating ECM patches – one showed that the patch studied was actually harmful to repair and the second suggested there was some benefit in larger tears. While there is not a lot of strong evidence to support routine use, further research and development is necessary to maximise this strategy

Aim. The demonstration of the in vivo bactericidal efficacy of a new bone cement with rifampicin contained in microcapsules and its intra-articular release profile. Method. Fifteen New Zealand White rabbits were employed to reproduce periprosthetic infection by intra-articular inoculation of 10. 5. CFU/mL of Staphylococcus aureus ATCC® 29213 using as a target implant a 3D printed stainless steel tibial insert. 7 days after inoculation, the first stage of the two stage exchange was carried out and at this time the animals were divided into two study groups: group C (7 rabbits) that received a spacer with gentamicin and group R (8 rabbits) that received a spacer with gentamicin and rifampicin microcapsules. Response to infection was monitored by clinical (weight and temperature), hematological (leukocyte, lymphocyte and platelet counts) and biochemical (erythrocyte sedimentation rate) analyses at the time of inoculation, at the first stage of exchange, 4 days after first stage and weekly until the fourth week when animals were euthanized. Microbiological counts were performed at the first stage of exchange and at the end of the study. Results. 14/15 animals (93.3%) developed a PJI 1 week after the inoculation. A statistically significant elevation of the leukocyte and platelet count and a decrease in the percentage of lymphocytes (p=0.0001) was found and positive microbiological cultures. Four weeks after the placement of the spacer, no bacterial growth was found in the soft tissue or bone samples of the group with rifampicin microcapsules (group R), being these differences statistically significant with p=0.01 and 0.03 respectively. The rifampicin intra-articular release kinetics showed concentrations above the staphylococcal MIC at all time points. Conclusions. The bone cement with microencapsulated rifampicin is effective in the in vivo treatment of prosthetic joint infection due to biofilm-forming S. aureus