Total Knee Joint Replacement Research Articles

Does standard post-operative rehabilitation have its place after total knee replacement?

The pilot study objective was to evaluate the effect of comprehensive post-operative physiotherapeutic treatment on the selected physiotherapeutic parameters as well as patients' quality of life after a total knee joint replacement surgery. Thirty patients after total knee joint arthroplasty were enrolled into the pilot study. After completing the physiotherapeutic processes, we have observed among the patients who underwent a total knee replacement surgery, a significant increase in muscle strength as with the flexors as well as the extensors (p = 0.001), improvement in their range of motion in knee joint flexion, in comparison to its range before treatment (p = 0.001), knee pain reduction (p = 0.001) and post-operative swelling (p <0.001), respectively. After undergoing the physiotherapeutic procedures, we recorded a statistically significant improvement in the monitored physical components: dressing (p = 0.008) and toilet use (p = 0.001), transfer from bed to chair (p = 0.008), walking on flat surface (p = 0.001), climbing stairs (p = 0.001). Passing the physiotherapy significantly reduced the degree of dependence of operated patients (p = 0.001). Early post-operative physiotherapy treatment positively affects patients' general condition. In addition, it improves muscle strength, range of motion of the operated joint, eliminates post-operative pain and reduces swelling that improves patients' self-sufficiency. Standard physiotherapy nowadays and in the next few years will take a unique place in patients' management after total knee joint replacement (Tab. 5, Ref. 26).

Sick leave in Sweden before and after total joint replacement in hip and knee osteoarthritis patients

Background and purpose — Little is know about patterns of sick leave in connection with total hip and knee joint replacement (THR and TKR) in patients with osteoarthritis (OA).Patients and methods — Using registers from southern Sweden, we identified hip and knee OA patients aged 40–59 years who had a THR or TKR in the period 2004–2012. Patients who died or started on disability pension were excluded. We included 1,307 patients with THR (46% women) and 996 patients with TKR (56% women). For the period 1 year before until 2 years after the surgery, we linked individual-level data on sick leave from the Swedish Social Insurance Agency. We created a matched reference cohort from the general population by age, birth year, and area of residence (THR: n = 4,604; TKR: n = 3,425). The mean number of days on sick leave and the proportion (%) on sick leave 12 and 24 months before and after surgery were calculated.Results — The month after surgery, about 90% of patients in both cohorts were on sick leave. At the two-year follow-up, sick leave was lower for both cohorts than 1 year before surgery, except for men with THR, but about 9% of the THR patients and 12–17% of the TKR patients were still sick-listed. In the matched reference cohorts, sick leave was constant at around 4–7% during the entire study period.Interpretation — A long period of sick leave is common after total joint replacement, especially after TKR. There is a need for better knowledge on how workplace adjustments and rehabilitation can facilitate the return to work and can postpone surgery.

Is there a risk of permanent renal dysfunction after primary total hip and knee joint replacements?

BackgroundPermanent renal dysfunction is considered as being a serious complication which may occur after major surgery and which furthermore may lead to increased morbidity and mortality. The objective of this study was to analyze the incidence of long-term postoperative renal dysfunction after primary total hip and knee joint replacements.MethodsLong-term postoperative renal dysfunction was analyzed in a retrospective study of 1301 consecutive primary total hip and knee joint replacements performed between January 2009 and December 2013. According to the RIFLE criteria, increased serum creatinine was an indicative of postoperative renal injury. The highest serum creatinine during the first postoperative week was chosen as a sign for maximum acute renal injury and was compared to the highest serum creatinine during the following 4–12 months.ResultsOne hundred and forty two patients with an increase in postoperative serum creatinine were included in the follow-up study. Six patients (4.2 %) died due to non-renal causes during the follow-up period. One patient died of severe renal injury, which was relatively very early postoperatively, and another patient had a rise in serum creatinine to 316 μmol/l during the follow-up period. All the remaining 132 patients (94 %) had full recovery with serum creatinine which returned to preoperative levels.ConclusionsThis study did not confirm that patients who underwent primary total hip and knee joint replacement surgery were at risk of developing permanent renal dysfunction up to 1 year after the index surgery.

Implementation of a Value-Driven Outcomes Program to Identify High Variability in Clinical Costs and Outcomes and Association With Reduced Cost and Improved Quality.

Transformation of US health care from volume to value requires meaningful quantification of costs and outcomes at the level of individual patients. To measure the association of a value-driven outcomes tool that allocates costs of care and quality measures to individual patient encounters with cost reduction and health outcome optimization. Uncontrolled, pre-post, longitudinal, observational study measuring quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist laboratory utilization, and management of sepsis. Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts. Total and component inpatient and outpatient direct costs across departments; cost variability for Medicare severity diagnosis related groups measured as coefficient of variation (CV); and care costs and composite quality indexes. From July 1, 2014, to June 30, 2015, there were 1.7 million total patient visits, including 34 000 inpatient discharges. Professional costs accounted for 24.3% of total costs for inpatient episodes ($114.4 million of $470.4 million) and 41.9% of total costs for outpatient visits ($231.7 million of $553.1 million). For Medicare severity diagnosis related groups with the highest total direct costs, cost variability was highest for postoperative infection (CV = 1.71) and sepsis (CV = 1.37) and among the lowest for organ transplantation (CV ≤ 0.43). For total joint replacement, a composite quality index was 54% at baseline (n = 233 encounters) and 80% 1 year into the implementation (n = 188 encounters) (absolute change, 26%; 95% CI, 18%-35%; P < .001). Compared with the baseline year, mean direct costs were 7% lower in the implementation year (95% CI, 3%-11%; P < .001) and 11% lower in the postimplementation year (95% CI, 7%-14%; P < .001). The hospitalist laboratory testing mean cost per day was $138 (median [IQR], $113 [$79-160]; n = 2034 encounters) at baseline and $123 (median [IQR], $99 [$66-147]; n = 4276 encounters) in the evaluation period (mean difference, -$15; 95% CI, -$19 to -$11; P < .001), with no significant change in mean length of stay. For a pilot sepsis intervention, the mean time to anti-infective administration following fulfillment of systemic inflammatory response syndrome criteria in patients with infection was 7.8 hours (median [IQR], 3.4 [0.8-7.8] hours; n = 29 encounters) at baseline and 3.6 hours (median [IQR], 2.2 [1.0-4.5] hours; n = 76 encounters) in the evaluation period (mean difference, -4.1 hours; 95% CI, -9.9 to -1.0 hours; P = .02). Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions.

Meta-analysis of epidural analgesia versus peripheral nerve blockade after total knee joint replacement.

Postoperative pain after major knee surgery can be severe. Our aim was to compare the outcomes of epidural analgesia and peripheral nerve blockade (PNB) in patients undergoing total knee joint replacement (TKR). Moreover, we aimed to compare outcomes of adductor canal block (ACB) with those of femoral nerve block (FNB) after TKR. We conducted a systematic search of electronic information sources, including MEDLINE; EMBASE; CINAHL; and the Cochrane Central Register of Controlled Trials (CENTRAL). We applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits in each of the above databases. Pain intensity assessed on visual analogue scale (VAS), nausea and vomiting, systolic hypotension, and urinary retention was the reported outcome parameters. We identified 12 randomised controlled trials (RCTs) comparing outcomes of epidural analgesia and PNB reporting a total of 670 patients. There was no significant difference between two groups in VAS scores at 0-12h (MD -0.48; 95% CI -1.07-0.11, P=0.11), 12-24h (MD 0.04; 95% CI -0.81-0.88, P=0.93), and 24-48h (MD 0.16; 95% CI -0.08-0.40, P=0.19). However, epidural analgesia was associated with significantly higher risk of postoperative nausea and vomiting (RR 1.65; 95% CI, 1.20-2.28, P=0.002), hypotension (RR 1.76; 95% CI, 1.26-2.45, P=0.0009), and urinary retention (RR 4.51; 95% CI, 2.27-8.96, P<0.0001) compared to PNB. Moreover, pooled analysis of data from 6 RCTs demonstrated no significant difference in VAS score between ACB and FNB at 24h (MD -0.00; 95% CI, -0.56-0.56, P=0.99) and 48h (MD -0.06; 95% CI, -0.14-0.03, P=0.23). PNB is as effective as epidural analgesia for postoperative pain management in patients undergoing TKR. Moreover, it is associated with significantly lower postoperative complications. ACB appears to be an effective PNB with similar analgesic effect to FNB after TKR. Future RCTs may provide better evidence regarding knee range of motion, length of hospital stay, and neurological complications.

Women's Experiences of Undergoing Total Knee Joint Replacement Surgery

The purpose of the study was to describe women's experiences of undergoing total knee joint replacement surgery. A qualitative approach was used. A content analysis of the text from interviews with five women was conducted. The time before surgery was marked by the experience of constant pain, which affected the women negatively in their everyday lives. During surgery, the information provided by the staff gave each woman a sense of security; the women handed over responsibility to the staff and experienced a sensation of relief. The postoperative period was characterized by a feeling of joy when the surgery was over, although a rough and tedious rehabilitation phase then began. Challenges in everyday life were a factor for motivation and confidence, although postoperative pain was experienced as discouraging. Support from health care staff is an important factor for coping with everyday life during the preoperative, perioperative and postoperative phases of undergoing knee joint replacement.

Does an Antibiotic-Loaded Hydrogel Coating Reduce Early Post-Surgical Infection After Joint Arthroplasty?

Background: Infection remains among the main reasons for joint prosthesis failure. Preclinical reports have suggested that antibacterial coatings of implants may prevent bacterial adhesion and biofilm formation. This study presents the results of the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating (Defensive Antibacterial Coating, DAC®) in patients undergoing hip or knee prosthesis.Methods: In this multicenter, randomized prospective study, a total of 380 patients, scheduled to undergo primary (n=270) or revision (n=110) total hip (N=298) or knee (N=82) joint replacement with a cementless or a hybrid implant, were randomly assigned, in six European orthopedic centers, to receive an implant either with the antibiotic-loaded DAC coating (treatment group) or without coating (control group). Pre- and postoperative assessment of clinical scores, wound healing, laboratory tests, and x-ray exams were performed at fixed time intervals.Results: Overall, 373 patients were available at a mean follow-up of 14.5 ± 5.5 months (range 6 to 24). On average, wound healing, laboratory and radiographic findings showed no significant difference between the two groups. Eleven early surgical site infections were observed in the control group and only one in the treatment group (6% vs. 0.6%; p=0.003). No local or systemic side effects related to the DAC hydrogel coating were observed, and no detectable interference with implant osteointegration was noted.Conclusions: The use of a fast-resorbable, antibiotic-loaded hydrogel implant coating can reduce the rate of early surgical site infections, without any detectable adverse events or side effects after hip or knee joint replacement with a cementless or hybrid implant.

Causes and incidence of 30 day hospital re-admissions after primary TKJR

Objective:30 day re-admission of patients following TKJR is estimated between 0.9-9.9%. It’s a cause of significant cost to the healthcare system and marks significant patient morbidity.Aim:The aim of this study is to describe the causes and incidence of patient re-admission to hospital within 30 days of a primary total knee joint replacement between 2009-2015 in a single centre.Methods:In a retrospective cohort study, computerized records were used to evaluated the causes and incidence of patient re-admission within 30 days of discharge following primary TKJR.Results:The total 30 day Re-admission rate was 5.0%. Medical causes for re-admission accounted for 29% of re-admissions. 34% were attributed to non-specific pain/swelling. Infection was attributed to 26%. 29% of patients presented with wound problems, either infective or non-infective. The total incidence of re-operation at 30 days was 0.77%.Conclusions:Our rate of re-admission is consistent with previous studies in the literature. Many patients were found to have no specific cause for re-admission. This suggests it may be possible to further reduce re-admission rates with improved patient education and management of common post-operative symptoms such as pain and swelling. Infection remains a common complication; fortunately the majority superficial infections are successfully treated with antibiotics and few requiring a washout operation. Medical complications account for almost a third showing the importance of good management of patient medical co-morbidities and risk factors.

CORR Insights(®): How Often Does Spindle Failure Occur in Compressive Osseointegration Endoprostheses for Oncologic Reconstruction?

Where Are We Now? For patients with a primary bone tumor of the lower extremity, limb-salvage surgery is the preferred approach when it is feasible to perform [4]. For patients undergoing distal-femur resections, endoprosthetic reconstructions allow immediate partial weight bearing and generally restore an acceptable level of limb function [9]. Traditional fixation approaches, including cement or press-fit intramedullary stems, depend in large measure on the amount of remaining bone into which the surgeon can anchor the device; the longer-term survivorship of these implants becomes critically dependent upon that sometimes-scarce resource. Among patients who survive for longer periods of time, aseptic loosening can result in additional disability and major surgery [6, 10]. Some patients simply do not have enough remaining host bone to allow secure fixation of the endoprosthesis. The Compress® Compliant Pre-stress implant (Biomet Inc, Warsaw, IN USA) was designed to promote osseointegration at the bone-prosthesis interface [2, 3, 8], particularly in patients with severe bone loss. In that setting, traditional cemented or cementless devices would have a high risk of failure. Compress® secures a titanium porous-coated spindle to the bone through a spring-loaded device anchored to a short-traction bar. A recent long-term outcome study demonstrated a survivorship of 80% using this fixation technique for distal femur implants [6]. However, little information has been reported analyzing the frequency of compressive osseointegration spindle failure in distal femoral reconstructions, nor have studies focused on the characteristics of rotational failure and the risk factors for this mechanical complication. While we have some insight into this important complication—patients with less remaining host bone seem to be at risk for it [5, 7]—a recent study that sought to attribute these failures to rotational stresses was unable to prove this contention, perhaps because of insufficient sample size [6]. Where Do We Need To Go? The present study showed that, while failures of compressive osseointegration implant do occur, and that spindle revision is sometimes called for, these events are uncommon and the overall survival rate from spindle failure is relatively high even at long-term followup. Injuries with a twisting mechanism produce the most rotational failures. It is recommended that we include antirotation pins at the fixation during the surgical procedure in order to prevent these failures. However, results from the current study showed that when omitting antirotational pins from surgery, the rate of rotational failures did not increase. More information is needed before we can properly determine whether to use antirotation pins. How Do We Get There? A future controlled study to determine the effect of these antirotation pins on the frequency of rotational failure is necessary in order to speak more definitively to this important unanswered question. Biomechanical studies should evaluate different stresses in heavy loading between stemmed implants (cemented and uncemented) and osseointegration implants. Results of such studies might also be applicable to the care of patients undergoing nononcological reconstructions, including revisions of traditional total hip, knee, or upper-extremity joint replacements.

YouTube Videos to Create a "Virtual Hospital Experience" for Hip and Knee Replacement Patients to Decrease Preoperative Anxiety: A Randomized Trial.

BackgroundWith declining reimbursement to health care systems, face-to-face time between patients and providers to optimize preoperative education and counseling may be challenging.ObjectiveBecause high patient anxiety prior to surgery has been linked to more severe and persistent pain after joint replacement surgery, the Orthopedic Surgery Department at Mayo Clinic in Florida created a playlist of 16 YouTube videos aimed at creating a virtual hospital experience for primary total hip and knee joint replacement patients. A randomized trial was then performed to evaluate the potential impact of viewing this playlist on preoperative anxiety.MethodsEach patient completed a Generalized Anxiety Disorder (GAD) score assessment at the time of the routine preoperative clinic visit and then randomized based on his/her gender, type of surgery, and initial GAD score to either the control group of standard education (education at face-to-face clinical visits as well as printed educational materials) or the treatment group (standard education plus access to the YouTube playlist). On the morning of the patient’s surgery, the same survey was repeated. Of the 65 patients who consented to participate in the study, 53 completed the study (82%) with 28 of 29 (97% completed) in the control group and 25 of 36 (69% completed) in the treatment group.ResultsOverall, the results showed a trend toward less anxiety in patients who viewed the YouTube videos; this was exhibited by a reduction in the median GAD score by 1 point. This trend is more clearly present in patients with high preoperative anxiety (predominantly women), as seen in the reduction of the median GAD score by 6 points in the treatment group.ConclusionsAlthough our experience is limited, our results indicate that a series of tailored videos may decrease patient anxiety preoperatively. We recommend further exploration of both this concept and the use of social media tools in preoperative patient education.Trial RegistrationClinicaltrials.gov NCT02546180; http://clinicaltrials.gov/ct2/show/NCT02546180 (Archived by WebCite at http://www.webcitation.org/6f6y0Dw7d).

(210) Prescribed pain medication before and after total joint replacement of hip or knee in Germany – a sickness fund analysis

(210) Prescribed pain medication before and after total joint replacement of hip or knee in Germany – a sickness fund analysis

Metabolomic analysis of human synovial fluid and plasma reveals that phosphatidylcholine metabolism is associated with both osteoarthritis and diabetes mellitus

This study was to investigate how OA patients with metabolic syndrome (MetS) are different metabolically from OA patients without MetS components and healthy individuals. A two-stage case–control study design was utilized. Synovial fluid (SF) and plasma samples were collected from patients undergoing total knee joint replacement due to primary OA and healthy controls (only plasma) and metabolically profiled using UPLC-MS coupled with assay kit which measures 186 metabolites. Orthogonal projection to latent structure-discriminant analysis and linear regression were used to identify metabolic markers for discriminating OA patients with MetS components from those without and healthy individuals. 54 paired SF and plasma samples from knee OA patients and 30 plasma samples from healthy controls were included in the discovery stage, and 143 plasma samples (72 from knee OA patients and 71 from the age, sex, and BMI matched controls) were included in the validation stage. OA patients with MetS can be clearly discriminated from OA patients without MetS based on the metabolite profiles of both SF and plasma and the separation appeared to be driven by type 2 diabetes but not obesity, hypertension, or dyslipidemia. When compared with OA patients with diabetes, OA without diabetes, and healthy controls, phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and phosphatidylcholine acyl-alkyl C36:3 (PC ae C36:3) were identified and confirmed to be associated with the concurrence of OA and diabetes (all p < 0.003). The study demonstrated that altered phosphatidylcholine metabolism was associated with both OA and diabetes mellitus.

前半程与全程使用止血带在膝关节置换术后失血与早期康复的对比

研究目的：研究完成假体安放后释放止血带与全程使用止血带在全膝关节置换术后失血与早期康复的对比。方法：本研究采用前瞻随机对照研究，选择2015年3月1日至2016年7月1日于青岛大学附属医院关节外科收入院，诊断均为左(或右)膝骨关节炎，并且初次行全膝关节置换术(TKA)者，术中分别将各50名符合纳入条件的患者随机分为2组：前半程使用止血带50例(前半程组)，全程使用止血带50例(全程组)。记录手术时间、术中出血量、围手术期的输血量、下肢深静脉血栓形成、肺栓塞人数，术后3天患肢膝上10 cm周径、术后7天VAS评分、HSS评分、产生张力性水泡例数、术后3天CPM功能锻炼度数、入院HCT、术后第一天引流量、HCT，术后第二天引流量、术后第三天HCT，并进行组间比较。结果：前半程组与全程组相比较，手术时间较长，术后第一、三天HCT值较高，术中失血量较多，术中红细胞丢失较多，总红细胞丢失量较少，隐性红细胞丢失量较少，术后第一、二天引流量少，患者术后1周HSS评分较高，术后3天患肢膝上10 cm周径较小，术后7天VAS评分较低，术后3天CPM达到的度数较大，产生张力性水泡的人数较少，差异均有统计学意义。而术后红细胞丢失量、显性红细胞丢失量差异无统计学意义。两组均无下肢静脉血栓、肺栓塞等并发症发生。结论：前半程应用止血带组相比较全程应用止血带组，不仅减少术后隐性红细胞丢失量及总红细胞丢失量，还利于患者早期恢复，且不增加发生下肢静脉血栓、肺栓塞等并发症的发生率，值得大家采纳。 Research Purpose: To compare the releasing tourniquet after prothesis placement using tourniquet during the whole-course in the case of hemorrhage resulting from total knee joint replacement and early rehabilitation. Method: Adopting prospective randomized controlled method, the research has taken the cases in the Surgical Department of Affiliated Hospital of Qingdao University from March 1, 2015 to July 1, 2016 as examples. Patients were diagnosed with left (right) knee osteoarthritis and the first time to receive total knee replacement (TKA). During operation 50 pa-tients were divided into two groups at random: the first half cases used 50 tourniquets (first half group), and patients using tourniquets during the whole course were 50 cases (whole course group). Duration of operation, bleeding volume in surgery, perioperative transfusion volume, deep vein thrombosis of the lower extremity, pulmonary embolism number, perimeter of 10 cm above knee 3 days after operation, VAS score of 7 days after operation, HSS score, number of tension vesicle cases, CPM functional exercise degree 3 days after operation, admission HCT, drainage volume on the 1st day after operation, and HCT 3 days after operation were recorded and compared between groups. Outcome: Compared with the whole course group, the first half group had longer duration of operation; HCT value was higher on the 1st and 3rd day of the operation; bleeding volume and amount of erythrocyte loss were larger during operation; total erythrocyte and hidden erythrocyte loss were less; drainage volume was less after the 1st and 2nd days of operation; patient’s HSS score was higher after a week of operation; perimeter of 10 cm above knee was smaller 3 days after operation; VAS score was lower 7 days after operation; CPM functional exercise degree reached higher 3 days after operation; number of tension vesicle cases was smaller; the differences were of statistical significance. Conclusion: Compared with the whole course group, using tourniquets in the first half group not only has reduced hidden erythrocyte loss and total erythrocyte loss, but also was beneficial to patients’ early recovery, dropping incidence rate of phlebothrombosis, pulmonary embolism and other complications. Therefore it is worth adopting.

Hemiarthroplasty of Hip-A prospective study for Conservation of Blood Loss

Background: Hemiarthroplasty of hip joint is a very commonly performed surgery. Several studies have been done which support the use of tranexamic acid in total knee joint replacements and few in total hip replacements. These studies have shown interesting positive results, but its benefits in hemiarthroplasty of hip joint have not yet widely known. This study aims to establish the role of tranexamic acid in reducing the intra and post-operative bleeding in case of hemiarthroplasty of hip. Material and Methods: This is a prospective study of thirty four patients who underwent hip hemiarthroplasty for fracture neck of femur. The patients were divided as treatment (Group A; n=17) and control (Group B; n=17) group. All the patients were alternatively assigned these two groups. In group A, the patients who underwent surgeries around hip joint were given a bolus dose of tranexamic acid intravenously 10mg/kg body weight about 10 minutes before starting skin incision and in group B, equal volume of normal saline was injected. Total blood loss during surgery was calculated by weighing the mops used and soiled by blood and measuring the volume of blood accumulated in suction apparatus used for the surgery. Pre and postoperative haemoglobin levels were compared. The volume of fluid accumulated in the post-operative suction drain was also recorded and the data collected were analysed. Results: The treatment group showed intra operative blood loss of 1000ml blood. Drain fluid after twenty four hours was 150ml only in one (5.9%). The difference in pre and post-operative Hb levels was

Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study.

BackgroundAutologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.Methods118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.ResultsBy 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.ConclusionsTreatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.

Effects of degeneration on the compressive and tensile properties of human meniscus

Healthy menisci function within the joint to prevent the underlying articular cartilage from excessive loads. Understanding how mechanical properties of menisci change with degeneration can drive future therapeutic studies to prevent this degeneration. Thus, the goal of this study was to characterize both compressive and tensile moduli of human menisci with varying degrees of gross damage due to osteoarthritis (OA). Twenty four paired menisci were collected from total knee joint replacement patients and the menisci were graded on a scale from 0–4 according to level of gross meniscal degeneration with 0=normal and 4=full tissue maceration. Each meniscus was then sectioned into anterior and posterior regions and subjected to indentation relaxation tests. Samples were sliced into 1mm thick strips, made into dumbbells using a custom punch, and pulled to failure. Significant decreases in instantaneous compressive modulus were seen in the lateral posterior region between grades 0 and 1 (36% decrease) and in the medial anterior regions between grades 1 and 2 (67% decrease) and 1 and 3 (72% decrease). Changes in equilibrium modulus where seen in the lateral anterior region between grades 1 and 2 (35% decrease), lateral posterior region between grades 0–2 (41% decrease), and medial anterior regions between grades 1 and 2 (59% decrease), 1 and 3 (67% decrease), 2 and 4 (54% decrease), and 3 and 4 (42% decrease). No significant changes were observed in tensile modulus across all regions and degenerative grades. The results of this study demonstrate the compressive moduli are affected even in early stages of gross degeneration, and continue to decrease with increased deterioration. However, osteoarthritic menisci retain a tensile modulus similar to that of previously reported healthy menisci. This study highlights progressive changes in meniscal mechanical compressive integrity as level of gross tissue degradation increases, and thus, early interventions should focus on restoring or preserving compressive integrity.

A1.4 Inflammatory microenvironment of rheumatoid and osteoarthritic joint affects immunomodulatory activity of adipose-derived mesenchymal stem cells

Background and objectives Adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory properties, but their activity is dependent on signals provided by local microenvironment. ASCs administration in rheumatoid arthritis (RA) did not bring consistent results, while in osteoarthritis (OA) it has beneficial effects. It is likely that proinflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs (RA-ASCs) and osteoarthritic ASCs (OA-ASCs) isolated from infrapatellar fat pad of the knee joint have been analysed. Materials and methods Infrapatellar fat pads were obtained from 29 RA and 12 OA patients undergoing total knee joint replacement surgery. Then, ASCs were isolated accordingly to routinely applied procedure. ASCs were treated or not with IFNγ or TNF. The expression of indoleamine 2,3-dioxygenase and heme oxygenase 1 mRNA was measured using quantitative PCR, while ASCs secretory potential was assessed by specific ELISAs. Rheumatoid synovial fibroblasts (RA-FLS) or peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured in ASC-conditioned media or co-cultured with ASCs. Next, cytokines secretion and cells proliferation were measured using ELISAs and bromodeoxyuridine/ 3 H-thymidine proliferation assays, respectively. Results RA- and OA-ASCs activity in vitro is comparable, nonetheless some differences in spontaneous secretory activity and heme oxygenase 1 mRNA expression have been observed. Unstimulated RA- and OA-ASCs slightly inhibited PBMCs proliferation and induced IL-10 secretion but increased IL-17A production and failed to suppress release of other proinflammatory factors (TNF, IFNγ, RANTES) by PBMCs. Under TNF stimulation, RA- and OA-ASCs up-regulated IL-6 and MMP-3 secretion in RA-FLS cultures and IL-17A release by PBMCs. ASCs treatment with IFNγ or TNF did not intensify their anti-inflammatory activity. Conclusions Our study demonstrates that immunosuppressive function of RA- and OA-ASCs derived from infrapatellar fat pad is impaired. Possibly, it is due to the localisation of ASCs in the site of inflammation. Moreover, TNF triggers proinflammatory properties of ASCs which indicates that when administered to the rheumatoid joint, ASCs may shift from an anti-inflammatory to proinflammatory phenotype. Acknowledgements This work was supported by the Polish National Science Centre (grant no. 2011/01/N/NZ5/00932) and by the European Union funds (European Social Fund, Human Capital Programme).

Positive impact of IGF-1-coupled nanoparticles on the differentiation potential of human chondrocytes cultured on collagen scaffolds.

PurposeIn the present study, silica nanoparticles (sNP) coupled with insulin-like growth factor 1 (IGF-1) were loaded on a collagen-based scaffold intended for cartilage repair, and the influence on the viability, proliferation, and differentiation potential of human primary articular chondrocytes was examined.MethodsHuman chondrocytes were isolated from the hyaline cartilage of patients (n=4, female, mean age: 73±5.1 years) undergoing primary total knee joint replacement. Cells were dedifferentiated and then cultivated on a bioresorbable collagen matrix supplemented with fluorescent sNP coupled with IGF-1 (sNP–IGF-1). After 3, 7, and 14 days of cultivation, cell viability and integrity into the collagen scaffold as well as metabolic cell activity and synthesis rate of matrix proteins (collagen type I and II) were analyzed.ResultsThe number of vital cells increased over 14 days of cultivation, and the cells were able to infiltrate the collagen matrix (up to 120 μm by day 7). Chondrocytes cultured on the collagen scaffold supplemented with sNP–IGF-1 showed an increase in metabolic activity (5.98-fold), and reduced collagen type I (1.58-fold), but significantly increased collagen type II expression levels (1.53-fold; P=0.02) after 7 days of cultivation compared to 3 days. In contrast, chondrocytes grown in a monolayer on plastic supplemented with sNP-IGF-1 had significantly lower metabolic activity (1.32-fold; P=0.007), a consistent amount of collagen type I, and significantly reduced collagen type II protein expression (1.86-fold; P=0.001) after 7 days compared to 3 days.ConclusionCollagen-based scaffolds enriched with growth factors, such as IGF-1 coupled to nanoparticles, represent an improved therapeutic intervention for the targeted and controlled treatment of articular cartilage lesions.

Popliteal Artery Thrombosis after Total Knee Replacement: An Unusual Complication.

Popliteal Artery Thrombosis after Total Knee Replacement: An Unusual Complication.

Expression profles of human CCN genes in patients with osteoarthritis or rheumatoid arthritis

ObjectiveOsteoarthritis (OA) and rheumatoid arthritis (RA) are widespread disabling joint disorders that are considered to be polygenic in nature. This study investigated the spatial expression patterns of all six known human CCN genes using end-stage OA and RA joint samples. Design We performed in situ hybridization and histologi-cal analysis to investigate the spatial expression patterns of human CCN genes using joint tissues obtained during total knee and hip joint replacement procedures on patients with advanced OA or RA. Normal joint tissues taken while performing bipolar hip replacement surgeries were used as controls. ResultsAll CCN genes were expressed at higher levels in OA and RA synovial samples as compared with normal controls. Whereas CCN3 and CCN6 were undetectable in control, OA, and RA cartilage, CCN1, CCN2, CCN4, and CCN5 were expressed to a greater extent in OA and RA knee cartilage. ConclusionsOur results indicate an involvement of several CCN genes in the pathophysiology of OA and RA.