Intra-articular Joint Space Research Articles

Effectiveness of Periarticular Infiltration of the Knee during Total Knee Arthroplasty for Postoperative Pain Management

Background: Different treatment regimens of analgesia, nerve blocks and epidurals are used for pain relief in Total Knee Arthroplasty (TKA). Local infiltration analgesia (LIA) is one of the modalities in which a cocktail combination of different medicines is infiltrated locally into the capsule, surrounding tissues or intraarticular joint space. This study aims to analyze the effectiveness of periarticular injection of combination drugs (Bupivacaine, Ketorolac and Morphine) during TKA for postoperative pain management.
 Methods: Total of 150 patients who underwent primary unilateral TKA were randomly categorized into 2 groups (75 each). Group A (control group) didn’t receive intraoperative periarticular injection but Group-B received the intraoperative injection of combined local analgesics and anaesthetics (Bupivacaine, Ketorolac and Morphine). Pain following surgery at 0, 1, and 2 postoperative days were recorded with visual analogue scale (VAS) whereas Knee Society Score was used to evaluate the pain and function pre-operative and 3 months’ post-operative. Statistical analysis was done using SPSS software.
 Results: Patients receiving periarticular infiltration of combination drugs intraoperatively had lower VAS for postoperative pain (p < 0.001) and this group also showed reduced need of analgesia postoperatively.
 Conclusions: Periarticular infiltration of knee during Total Knee Arthroplasty is effective in management of postoperative pain
 Keywords: Periarticular; Total Knee Arthroplasty; combination drugs; postoperative pain

Comparative Observational Study on the Effects of Intra-articular Hominis Placenta Pharmacopuncture and Acupoint Hominis Placenta Pharmacopuncture for Knee Osteoarthritis Patients

The aim of this case report was to observe the effects of intra-articular hominis placenta pharmacopuncture (HPP). Based on the medical records patients who received intra-articular treatment or received acupoint pharmacopuncture treatment, a comparison was made. There were 35 patients who were hospitalized for degenerative osteoarthritis of the knee joint from the 1<sup>st</sup> October 2019 to 26<sup>th</sup> September 2020. There were 14 patients who were treated with HPP in the intra-articular joint space (Group A), and 14 patients who were treated with HPP at specific acupoints (Group B). The outcome effects were measured using the Korean Western Ontario and Mc (KWOMAC) the visual analog scale (VAS) before the first treatment, and after the fifth treatment. The KWOMAC (<i>p</i> < 0.001) and the VAS scores (<i>p</i> < 0.001) in Groups A and B significantly improved after treatment compared with before treatment. When comparing Group A improvement with Group B improvement using the KWOMAC there was no statistically significant difference however, when using the VAS scores, Group A treatment was statistically more effective compared with Group B (<i>p</i> = 0.002). This study indicated that HPP may be an effective treatment for knee osteoarthritis. Moreover, intra-articular HPP may be more effective than acupoint HPP for knee osteoarthritis.

Recent advances in targeted drug delivery for treatment of osteoarthritis.

Osteoarthritis is associated with severe joint pain, inflammation, and cartilage degeneration. Drugs injected directly into intra-articular joint space clear out rapidly providing only short-term benefit. Their transport into cartilage to reach cellular targets is hindered by the tissue's dense, negatively charged extracellular matrix. This has limited, despite strong preclinical data, the clinical translation of osteoarthritis drugs. Recent work has focused on developing intra-joint and intra-cartilage targeting drug delivery systems (DDS) to enable long-term therapeutic response, which is presented here. Synovial joint targeting hybrid systems utilizing combinations of hydrogels, liposomes, and particle-based carriers are in consideration for pain-inflammation relief. Cartilage penetrating DDS target intra-cartilage constituents like aggrecans, collagen II, and chondrocytes such that drugs can reach their cellular and intra-cellular targets, which can enable clinical translation of disease-modifying osteoarthritis drugs including gene therapy. Recent years have witnessed significant increase in both fundamental and clinical studies evaluating DDS for osteoarthritis. Steroid encapsulating polymeric microparticles for longer lasting pain relief were recently approved for clinical use. Electrically charged biomaterials for intra-cartilage targeting have shown promising disease-modifying response in preclinical models. Clinical trials evaluating safety of viral vectors are ongoing whose success can pave the way for gene therapy as osteoarthritis treatment.

Retaining the medial collateral ligament in high tibial medial open-wedge osteotomy mostly results in post-operative intra-articular gap reduction.

The current study aimed to evaluate how open-wedge high tibial osteotomy (OWHTO) without the release of medial collateral ligament (MCL) changes in vivo intra-articular joint space after the surgery. Patients with varus malalignment of the knee with an indication for OWHTO were included in this study. The intra-articular gap was measured before and 30min after OWHTO without MCL release using a series of calibrated nerve hooks. The association of post-operative gap size with varus angle, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA) and joint line convergence angle (JLCA) was also assessed. A total of 42 knees from 38 patients were evaluated. The mean size of the intra-articular gap of the medial compartment was 5.2 ± 1mm before the osteotomy and 3.1 ± 2.2mm at 30min post-osteotomy. The size of the intra-articular gap decreased post-operatively in 30 knees (71.5%), increased in eight knees (19%) and remained the same in the remaining four knees (9.5%). Smaller MPTA and more correction were associated with a decrease in gap size after the osteotomy (p = 0.01 and p = 0.03, respectively). A significant negative correlation was observed between the correction size and the gap size after osteotomy (r = - 0.317, p = 0.04). Intra-articular pressure of the medial compartment increases in the majority of cases following OWHTO without MCL release. Until the factors affecting this increased pressure are thoroughly identified, MCL release seems to be a wiser option during OWHTO. III.

Injectable liquid polymers extend the delivery of corticosteroids for the treatment of osteoarthritis

Drug delivery strategies generally use inert materials, such as high molecular weight polymers, to encapsulate and control the release rate of therapeutic drugs. Diffusion governs release and depends on the ease of permeation of the polymer alongside the device thickness. Yet in applications such as osteoarthritis, the physiological constraints and limited intra-articular joint space prevent the use of large, solid drug delivery implants. Other investigators have explored the use of micro- and nanoparticle drug delivery systems. However, the small size of the systems limits the total drug that may be encapsulated and its short diffusion distance causes rapid release. Ordinarily, the extremely low diffusivity of a polymer fluid would make this an unsuitable delivery system. Our technology takes advantage of specific molecular interactions between drug and polymer, which can control the rate of release beyond diffusion. With this “affinity-based drug delivery”, we have shown that delivery rates from solid polymer can be prolonged from hours and days, to weeks and months. In this paper, we demonstrate that this affinity-based mechanism also applies to low diffusivity fluid-phase polymers. They show release rates that are substantially slower than chemically similar polymers incapable of forming those inclusion complexes. The similarity of this study's liquid polymers to the viscoelastic fluids used in current clinical practice makes it an ample delivery system for osteoarthritic application. We confirmed the capacity of anti-inflammatory delivery of corticosteroids: hydrocortisone, triamcinolone, and dexamethasone; from both solid implants and polymer fluids. Further, we demonstrated that viscoelastic properties are widely tunable, and within the range of native synovial fluid. Lastly, we determined these polymer fluids have no impact on the differentiation of mesenchymal stem cells to cartilage and are not cytotoxic to a common cell line.

Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial.

Adipose‐derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra‐articular joint space. Culture‐expanded human AMSCs grown in human platelet‐lysate were delivered via intra‐articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x‐ray, magnetic resonance imaging, and histopathology. Intra‐articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra‐articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910–922

Safety of Intra-Articular Implantation of Oligo[Poly(ethylene glycol) Fumarate] Scaffolds into the Rabbit Knee.

Implantable biomaterials supporting extended release of pharmacologic agents may permit localized intra-articular delivery of drugs that modulate the fibrotic response to injuries and surgery. Oligo[poly (ethylene glycol)] fumarate (OPF) is an attractive organic carrier, but its safety profile within synovial joints remains unclear. Here, we assessed the safety of OPF sponges using a validated in vivo model of knee arthrofibrosis. A cohort of 102 rabbits was divided into five groups: arthrotomy only (24), arthrotomy with OPF scaffold placement (24), surgically induced contracture (24), surgically induced contracture with OPF scaffold placement (24), and control without any surgical intervention (6). Six rabbits per surgical group were sacrificed at 72 h, 2, 8, and 24 weeks. Outcomes included biomechanical testing of range of motion, histologic analysis of synovial and cartilage tissues, and scaffold degradation. Cartilage histology and biomechanical measurements were comparable between groups with and without OPF. Synovial inflammation scores were similar among most groups with a minimally elevated score in the rabbits with arthrotomy and OPF versus those with arthrotomy alone. Scores for synovial tissues in rabbits with contracture and OPF were clinically equivalent to those with contractures alone. Most animals (92%) retained scaffold fragments at 24 weeks. Thus, OPF scaffolds implanted into native or arthrofibrotic rabbit knees neither induce nor aggravate cartilage damage, synovial inflammation, or contractures. The apparent safety of OPF scaffolds suggests that they are suitable carriers for the controlled delivery of reagents into the intra-articular joint space to treat arthrofibrosis.

Knee Osteoarthritis Treated with Percutaneous Chondral-Bone Interface Optimization: A Pilot Trial

Objective: The objective is to evaluate the efficacy of using tibial bone marrow delivered to the chondral-bone interface (CBI) via percutaneous chondral bone interface optimization (PeCaBoo) as a therapy for knee osteoarthritis (OA). Study Design: A series of prospective cases were presented. Participants: Our study included 10 patients with medial or lateral compartment knee OA. Methods: With 1 cc of heparin pre-loaded in the syringe, 5 cc of tibial bone marrow was withdrawn from the proximal tibia. The resultant 6 cc of aspirate in the syringe was injected via PeCaBoo, 2 cc at a time, into the superior CBI and inferior CBI. The remaining 2 cc was injected via needle into the intra-articular joint space. Main Outcome Measurements: Patients had MRIs taken pre-procedure and 3 months post-procedure to measure bone edema and intra-articular matrix thickness. Patient-reported outcomes recorded included the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Numeric Paint Rating Scale (NRS), which were both obtained pre-procedure and post-procedure at 3, 6, and 12 months. Use of non-steroidal anti-inflammatories (NSAIDs) was recorded pre- and post-procedure as well. Results: Our study included 4 males and 6 females, with an average age of 63.5 years. The average follow-up time was 14 months, with a range of 13 - 15 months. The mean WOMAC score was 58.2 points pre-procedure and 35.3 points post-procedure (p Boo procedure. The subgroup of patients with tibial edema and knee OA had optimal outcomes. Conclusions: Tibial bone marrow stem cell delivered via PeCaBoo is a novel minimally-invasive treatment for knee OA, with potential to repair cartilage and improve knee pain and function.

Open-MRI measures of cam intrusion for hips in an anterior impingement position relate to acetabular contact force.

Open MRI in functional positions has potential to directly and non-invasively assess cam femoroacetabular impingement (FAI). Our objective was to investigate whether open MRI can depict intrusion of the cam deformity into the intra-articular joint space, and whether intrusion is associated with elevated acetabular contact force. Cadaver hips (9 cam; 3 controls) were positioned in an anterior impingement posture and imaged using open MRI with multi-planar reformatting. The β-angle (describing clearance between the femoral neck and acetabulum) was measured around the entire circumference of the femoral neck. We defined a binary "MRI cam-intrusion sign" (positive if β < 0°). We then instrumented each hip with a piezoresistive sensor and conducted six repeated positioning trials, measuring acetabular contact force (F). We defined a binary "contact-force sign" (positive if F > 20N). Cam hips were more likely than controls to have both a positive MRI cam-intrusion sign (p = 0.0182, Fisher's exact test) and positive contact-force sign (p = 0.0083), which represents direct experimental evidence for cam intrusion. There was also a relationship between the MRI cam-intrusion sign and contact-force sign (p = 0.033), representing a link between imaging and mechanics. Our findings indicate that open MRI has significant potential for in vivo investigation of the cam FAI mechanism.

Computed tomography arthrography with traction in the human hip for three-dimensional reconstruction of cartilage and the acetabular labrum

To develop and demonstrate the efficacy of a computed tomography arthrography (CTA) protocol for the hip that enables accurate three-dimensional reconstructions of cartilage and excellent visualization of the acetabular labrum. Ninety-three subjects were imaged (104 scans); 68 subjects with abnormal anatomy, 11 patients after periacetabular osteotomy surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent diluted with lidocaine was injected using a lateral oblique approach. A Hare traction splint applied traction during CT. The association between traction force and intra-articular joint space was assessed qualitatively under fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30 subjects; the maximum joint space under traction was measured. Using the Hare traction splint, the intra-articular space and boundaries of cartilage could be clearly delineated throughout the joint; the acetabular labrum was also visible. Dysplastic hips required less traction (∼5 kg) than normal and retroverted hips required (>10 kg) to separate the cartilage. An increase in traction force produced a corresponding widening of the intra-articular joint space. Under traction, the maximum width of the intra-articular joint space during CT ranged from 0.98-6.7 mm (2.46 ± 1.16 mm). When applied to subjects with normal and abnormal hip anatomy, the CTA protocol presented yields clear delineation of the cartilage and the acetabular labrum. Use of a Hare traction splint provides a simple, cost-effective method to widen the intra-articular joint space during CT, and provides flexibility to vary the traction as required.

Distance between parapatellar portal and intra-articular space for needle positioning in knee osteoarthritis

Background: Intra-articular injection is a common therapeutic procedure in osteoarthritis (OA) that need high accuracy. This study was aimed to measure the distance between parapatellar skin and intra-articular space as a guidance to choose the length of needle needed to perform intra-articular injection. Methods: Twenty one knees MRI were taken from 16 females with knee osteoarthritis. The length of the needle needed to reach intra-articular space was reconstructed by drawing straight line from skin to intra-articular fluid. Paired t-test was using to analyze the mean difference of measurement of left side compare with right side with significant indicator if p-value < 0.05. Results: The entry point on both medial and lateral parapatellar were more cranial than transverse mid-patellar line. On medial portal, the closest distance from skin to intra-articular space is 27.81 ± 7.58 mm. Mean point of entry is 4.46 ± 2.16 mm cranial to mid-patellar line, and 14.20 ± 4.45 mm posterior to the prominence of medial border of patella. On lateral portal, the closest distance from skin to intra-articular space is 16.84 ± 6.79 mm. Mean point of entry is 11.10 ± 5.94 mm cranial to mid-patellar line, and 8.91 ± 3.83 mm posterior to the prominence of lateral border of patella. Conclusion: MRI knee osteoarthritis study showed that the mean distance between skin and intra-articular joint space of medial portal is 27.81 ± 7.58 mm, and lateral portal is 16.84 ± 6.79 mm. The portals on both sides is cranial to midpoint of patella, lateral appears more proximal than medial. This should be put into consideration in choosing needle length and portal projection to increase intra-articular injection accuracy. (Med J Indones. 2013;22:83-7) Keywords: Needle length, osteoarthritis, parapatellar skin portal

The effect of cooling on coagulation and haemostasis: Should “Ice” be part of treatment of acute haemarthrosis in haemophilia?

Repeated haemarthroses and the consequences of blood in the joint contribute to blood induced joint disease (BIJD) in people with haemophilia (PWH). Prevention of bleeding, through medical management, is the standard of care in developed countries, but is not universally available due to financial and other barriers. Ice application, as part of R.I.C.E. (Rest, Ice, Compression, Elevation) or alone, is commonly recommended as an adjunct treatment to decrease bleeding, pain, tissue metabolism, oedema, and inflammation. This article will review evidence regarding local cooling by commonly used ice application methods, to decrease the temperature of the skin and intra-articular (IA) joint space and the resultant effects on haemostasis and coagulation. The general literature was reviewed for articles in English describing temperatures achievable in the skin and IA space using clinically relevant ice protocols, and the effect of cooling on haemostasis and coagulation. The literature demonstrates that typical methods of ice application can cool both the skin and IA space. Published, general literature studies have also consistently demonstrated that experimental cooling of blood and/or tissue, both in vitro and in vivo in humans and in animal models, can significantly impair coagulation and prolong bleeding. In PWH with acute haemarthrosis, ice application has potential to increase haemorrhage morbidity by further impairing coagulation and haemostasis. Ice has not been shown to improve overall outcome, stop bleeding nor swelling from haemarthrosis. Although ice can help manage acute, haemarthrosis-related pain, there are other available interventions that will not impair coagulation and haemostasis.

Clinical utility of ultrasound guidance for intra-articular knee injections: a review

Intra-articular corticosteroid and hyaluronic acid injections provide short-term symptom amelioration for arthritic conditions involving structural damage or degenerative changes in the knee. Conventional palpation-guided anatomical injections frequently result in inaccurate needle placement into extra-articular tissue and adjacent structures. The purpose of this review was to determine the effect of ultrasound guidance on the accuracy of needle placement, clinical outcomes, and cost-effectiveness in comparison with anatomical landmark-guided intra-articular large joint injections, with particular emphasis on the knee. A total of 13 relevant studies were identified; five studied the knee, seven studied the shoulder, one used both the knee and shoulder, and none studied the hip. Ultrasound was used in seven studies; the remaining studies utilized air arthrography, fluoroscopy, magnetic resonance arthrography, or magnetic resonance imaging. Across all studies (using all imaging modalities and all joints), needle placement accuracy ranged from 63% to 100% with ultrasound and from 39% to 100% with conventional anatomical guidance. Imaging guidance improved the accuracy of intra-articular injections of the knee (96.7% versus 81.0%, P < 0.001) and shoulder (97.3% versus 65.4%, P < 0.001). In particular, ultrasound guidance of knee injections resulted in better accuracy than anatomical guidance (95.8% versus 77.8%, P < 0.001), yielding an odds ratio of 6.4 (95% confidence interval 2.9–14). Ultrasound guidance notably improves injection accuracy in the target intra-articular joint space of large joints including the knee. The enhanced injection accuracy achieved with ultrasound needle guidance directly improves patient-reported clinical outcomes and cost-effectiveness.

A Mass in the Temporomandibular Joint

A 55-year-old woman with a three-year history of progressive migraine headaches developed a rightsided posterior open bite and right preauricular facial swelling. Several primary and specialty medical and dental practitioners evaluated her case and made a diagnosis of intractable migraine headaches. Because of her progressive symptoms, she had been referred to the Division of Oral and Maxillofacial Surgery, Mayo Clinic (Rochester, Minn.), for further evaluation. The patient’s medical and surgical histories were unremarkable, including any history of facial trauma. Her facial pain and migraines had been treated with a range of overthe-counter and prescription analgesics, with limited success. At examination, the patient had a mild degree of right-sided preauricular facial swelling that was mildly painful to palpation and was associated with a malocclusion of approximately 3 millimeters on the right side and a posterior open bite with continued and progressive ipsilateral headaches. Panoramic plain radiography showed a spaceoccupying lesion in the right temporomandibular joint (TMJ) (Figure 1). A computed tomographic scan with intravenous contrast material disclosed a hypoattenuated mass occupying the right TMJ space, with cortical erosion and destruction of the glenoid fossa (Figure 2). The cortical architecture of the temporomandibular condyle was well-preserved, although it was displaced significantly and inferiorly, leading to the development of malocclusion. Cranial nerves were grossly intact, with no evidence of neurologic deficit in the trigeminal or facial nerve distributions. There was no evidence of involvement of the middle ear canal, and hearing was preserved. In the absence of a histologic diagnosis, the treating surgeon (D.K.) performed a right TMJ arthroplasty for open joint exposure and exploration. Upon entry into the TMJ space, the surgeon noted a large volume of cartilaginous foreign bodies in the intra-articular joint space. The articular surface of the mandibular condyle appeared to be wellpreserved; however, there was significant erosion and disruption of the glenoid fossa superiorly, with a small focus of intracranial extension. Despite a limited dural exposure, there was no significant cranial extension or cerebrospinal fluid leak. After removing the tumor, the surgeon repositioned the mandibular condyle within the glenoid fossa, resulting in improved occlusion. A mass in the temporomandibular joint

Frictional properties of Hartley guinea pig knees with and without proteolytic disruption of the articular surfaces

To apply a pendulum technique to detect changes in the coefficient of friction of the articular cartilage of the intact guinea pig tibiofemoral joint after proteolytic disruption. Twenty-two hind limbs were obtained from 11 3-month old Hartley guinea pigs. Twenty knees were block-randomized to one of two treatment groups receiving injections of: (1) alpha-chymotrypsin (to disrupt the superficial layer of the articular surface) or (2) saline (sham; to control for the effects of the intra-articular injection). The legs were mounted in a pendulum where the knee served as the fulcrum. The decay in pendulum amplitude as a function of oscillation number was first recorded and the coefficient of friction of the joint was determined from these data before injection. Ten microliters of either isotonic saline or 1 Unit/microL alpha-chymotrypsin was then injected into the intra-articular joint space and incubated for 2h. The pendulum test was repeated. Changes in the coefficient of friction between the sham and alpha-chymotrypsin joints were compared. One additional pair of knees was used for histological study of the effects of the injections. Treatment with alpha-chymotrypsin significantly increased the coefficient of friction of the guinea pig knee by 74% while sham treatment decreased it by 8%. Histological sections using Gomori trichrome stain verified that the lamina splendens was damaged following treatment with alpha-chymotrypsin and not following saline treatment. Treatment with alpha-chymotrypsin induces mild cartilage surface damage and increases the coefficient of friction in the Hartley guinea pig knee.

Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced th2activity.

Gene therapy has been explored as a potential method for treating chronic inflammatory diseases such as rheumatoid arthritis. To determine the efficacy of intra-articular IL-4 gene therapy in an animal model of arthritis using a retroviral vector, a retrovirus encoding rat IL-4 (DA-IL-4) was engineered, purified and concentrated to high titer (>/=109 CFU/ml). Infectivity and expression levels were demonstrated in vitro using cultured fibroblast-like synoviocytes. Efficacy was evaluated in the rat adjuvant arthritis model. DA-IL-4 or DA-beta-gal retrovirus was injected into the intra-articular joint space of the right ankle on day 12 after immunization. Three days after joint injection, the injected paw contained increased levels of IL-4 compared with control or with the contralateral uninjected paw, demonstrating successful transgene expression. Surprisingly, 8 days after treatment IL-4 levels continued to increase in the injected and contralateral paw compared with DA-beta-gal-treated animals. Serum IL-4 levels were also elevated in DA-IL-4-treated rats. RT-PCR studies demonstrated that the transgene was expressed in the injected ankle but not in the contralateral joint. IL-4 gene therapy resulted in a significant reduction in paw swelling and decreased radiographic evidence of bone destruction. This is the first demonstration of successful intra-articular retroviral gene treatment using a therapeutic gene. In addition to its anti-inflammatory effect, this study supports the potential application of intra-articular gene therapy as a method for enhancing systemic Th2 function.