Novel use of motor-sparing genicular nerve blocks for knee injuries in the emergency department.

Knee injuries are quite prevalent in the Emergency Department (ED) and often present with severe pain, necessitating effective pain management strategies. Traditional pain management approaches, including opioid medications, may carry undesirable side effects and potential risks, leading to the growing interest in non-opioid alternatives. Nerve blocks have emerged as promising options for targeted pain relief in the ED. Motor-sparing nerve blocks have gained importance due to their ability to provide effective analgesia without compromising motor function [1]. The case series demonstrates the successful use of ultrasound-guided genicular nerve blocks(GNB) in the Emergency Department, providing targeted pain relief without compromising motor function. GNBs offer a valuable alternative to traditional nerve blocks(femoral, fascia iliaca, adductor canal) and opioid-based pain control strategies in the ED. As the evidence base grows, GNBs may become a more established component of ED pain management protocols, enhancing patient outcomes and safety in the management of acute knee injuries. The incorporation of ultrasound-guided motor-sparing nerve blocks in ED pain management protocols may hold great promise in optimising pain control and enhancing patient comfort. Trial Registration: N/A.

E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis.

Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8-week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches.

Inflammation plays a central role in the pathogenesis of knee PTOA after knee trauma. While a comprehensive therapy capable of preventing or delaying post-traumatic osteoarthritis (PTOA) progression after knee joint injury does not yet clinically exist, current literature suggests that certain aspects of early post-traumatic pathology of the knee joint may be prevented or delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted therapeutic approaches that may be capable of effectively reducing the continuous cycle of inflammation and concomitant processes that lead to cartilage degradation as well as those that can simultaneously promote intrinsic repair processes. Within this context, we focus on early disease prevention, the optimal timeframe of treatment and possible long-lasting sustained delivery local modes of treatments that could prevent knee joint-associated PTOA symptoms. Specifically, we identify anti-inflammatory candidates that are not only anti-inflammatory but also anti-degenerative, anti-apoptotic and pro-regenerative.

A woman in her sixties with a knee injury after a fall. / En kvinne i 60-årene med kneskade etter fall.

BACKGROUND: The diagnosis of necrotising soft tissue infections (NSTIs, necrotising fasciitis, myositis and cellulitis) may be clinically challenging, and can result in fatal outcomes. CASE PRESENTATION: A previously healthy woman in her sixties fell and cut her right patella. The wound was complicated by localised infection, which subsequently developed into a bacterial bursitis. She responded to intravenous antibiotics and was followed up at the outpatient clinic. Nineteen days later she was admitted with the same symptoms and clinical presentation as at the previous admission. She was started on the same antibiotics based on the last prepatellar bursal fluid culture. This time, however, she became systemically impaired and septic. Many differential diagnoses were suspected, and she was repeatedly examined with the aid of blood samples, blood cultures, knee joint and prepatellar bursal punctures, and ultrasound scans. The patient's right lower extremity became swollen and was further examined with a CT scan, giving rise to suspicion of an NSTI. Ultimately four surgical revisions were performed (fasciotomy) in addition to continuous administration of antibiotics, fluid and pressor treatment. Biopsies of the fascia, muscle and fatty tissue were secured for microscopy, culture and histology. Unfortunately the patient died and histology confirmed necrotising fasciitis. INTERPRETATION: NSTIs are aggressive infections with dismal outcomes. This case illustrates the importance of clinical suspicion of this diagnosis, also in healthy patients. Immediate treatment with surgical debridement and intravenous antibiotics is crucial.

Ultrasound-guided injection for the diagnosis and treatment of posteromedial knee friction syndrome.

OBJECTIVE: To describe an ultrasound guided injection technique for diagnosing and treating posteromedial knee friction syndrome, which occurs between the sartorius/gracilis tendons and medial femoral condyle (MFC). MATERIALS AND METHODS: Our study was IRB-approved and HIPAA-compliant. We identified patients via a retrospective review of medical records and MRI with posteromedial knee pain and isolated edema between MFC and sartorius/gracilis tendons and no evidence for meniscal tear, ruptured Baker's cyst or degenerative joint disease. Patients were referred for an ultrasound-guided procedure to inject anesthetic and corticosteroid at the site of edema. Procedures were evaluated for technical success, which was defined as satisfactory identification of the injection site and adequate delivery of medication. Follow-up was available up to 8 weeks after the procedure to determine the response and any potential complications. RESULTS: Fourteen subjects with MRI and symptoms of posteromedial knee friction syndrome underwent 14 injections. Technical success was achieved in all procedures, with no complications. At 8 weeks' follow-up, 92% of patients had symptom improvement. VAS before and 8 weeks after the procedure changed from 5.2 ± 2.7 to 0.9 ± 2.1 (p = 0.0002), respectively. CONCLUSION: Ultrasound-guided injection of edema between the MFC and sartorius/gracilis tendons supports the diagnosis of a posteromedial knee friction syndrome and successfully treats its associated symptoms.

[Damage to periarticular soft tissues in real clinical practice: frequency, nature, effectiveness of non - steroidal anti - inflammatory drugs].

Damage to periarticular soft tissues is a common pathology that causes severe pain and impaired function of the musculoskeletal system. AIM: To determine the frequency, nature and clinical features of damage to periarticular soft tissues in real clinical practice, as well as the effectiveness of non - steroidal anti - inflammatory drugs (NSAIDs) in the debut of treatment of this pathology. MATERIALS AND METHODS: During the observational study, the frequency of defeat of the periarticular soft tissues in the structure of visits to 68 outpatient orthopedic surgeons in different cities of Russia for 1 month was estimated. Assessed the nature and dynamics of clinical manifestations during treatment in 1227 patients with defeat of the periarticular soft tissues. NSAIDs, mainly the original meloxicam, were used as a "first line" treatment for damage of the periarticular soft tissues. The results of treatment were evaluated after 10-14 days at a repeat visit of patients. RESULTS: The proportion of patients with damage of the periarticular soft tissues was 15.8% of the total number of people who applied for outpatient care. Among 1227 patients (men 57.5%, average age 51.3±15.5 years) who were observed in the dynamics, prevailed were those with damage of the periarticular soft tissues of the knee joint area (knee joint enthesopathy, prepatellar bursitis, tendonitis/ bursitis of the goose foot area) - 21.2%, feet (plantar fasciitis, calcaneal spur) - 16.9%, shoulder (tendonitis of the muscles of the shoulder rotators) - 16.4% and the elbow (lateral and medial epicondylitis) - 15.3%. During treatment, there was a significant decrease in the total severity of pain - from 6.58±1.61 to 2.48±1.60 points on an 11-point numerical rating scale (p.

The infrapatellar fat pad is affected by injury induced inflammation in the rabbit knee: use of dexamethasone to mitigate damage.

OBJECTIVE AND DESIGN: The health of the infrapatellar fat pad (IFP) has been linked to pain, joint inflammation, and the onset of post-traumatic osteoarthritis. Thus, early inflammation effects on the IFP could have long term sequelae on joint integrity. This study was designed to characterize the natural history of the IFP in a model of surgically induced knee injury and inflammation, and to test the efficacy of one intra-articular (IA) administration of dexamethasone (DEX) immediately following surgery. METHODS: An IA bone drill hole injury to the rabbit knee was conducted and immediately treated with DEX (n = 12). Early and late post-surgical time-points were investigated (48 h and 9 weeks) and the outcome measures were analysis of IFP histology, mRNA levels for relevant molecules, and protein levels for a subset of cytokines. Data were analyzed against a surgical control (injury without treatment; n = 12), a surgical sham (capsular incision only; n = 12), and normal control (n = 6). TREATMENT: Single IA injection of DEX (0.5 mg/kg), administered at the completion of surgery. RESULTS: IFPs from injured joints exhibited significantly increased cellularity and early fibrosis at 48 h post surgery. While the histological inflammation from a capsular incision alone resolved, knee injured animals progressed to a significantly more fibrotic IFP by 9 weeks. DEX significantly lowered histological scores at 48 h, but not at the 9 weeks. DEX did not influence mRNA levels for IL-1ß, 6, and 8, however, protein analysis indicated that IL-8 levels were lower in DEX treated joints. DEX resulted in significantly elevated expression of mRNA for MCP-1, leptin, and VEGF. CONCLUSION: One IA administration of a glucocorticoid appears to mitigate the initial inflammation within the joint, but is not sufficient to protect the joint to 9 weeks post-surgery.

Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats.

UNLABELLED: The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee. METHODS: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 µg/kg), progesterone (4mg) and testosterone (125 & 250µg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively. RESULTS: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms. DISCUSSION: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee. CONCLUSION: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.

Prevention of cartilage degeneration and gait asymmetry by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.

OBJECTIVE: To investigate whether cartilage degeneration is prevented or minimized in a rat model of anterior cruciate ligament (ACL) injury following a single dose-escalated intraarticular injection of lubricin derived from human synoviocytes in culture. METHODS: Unilateral ACL transection (ACLT) of the right hind limb was performed in Lewis rats (n = 56). Control animals underwent a capsulotomy alone, leaving the ACL intact (n = 11). Intraarticular injections (50 µl/injection) of phosphate buffered saline (PBS; n = 14 rats) and human synoviocyte lubricin (1,600 µg/ml; n = 14 rats) were performed on day 7 postsurgery. Animals were killed on day 70 postsurgery. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. Urinary C-telopeptide of type II collagen (CTX-II) levels were measured on days 35 and 70 postsurgery. Hind limb maximum applied force was determined using a variable resistor walkway to monitor quadruped gait asymmetries. RESULTS: Increased immunostaining for lubricin in the superficial zone and on the surface of cartilage was observed in lubricin-treated and control animals but not in PBS-treated or untreated animals with ACLT. On days 35 and 70 after surgery, urinary CTX-II levels in human synoviocyte lubricin-treated animals were lower than in untreated and PBS-treated animals (P < 0.005 and P < 0.001, respectively). Animals with ACLT treated with human synoviocyte lubricin and control animals distributed their weight equally between hind limbs compared to PBS-treated or untreated animals (P < 0.01). CONCLUSION: Our findings indicate that a single intraarticular injection of concentrated lubricin following ACLT reduces type II collagen degradation and improves weight bearing in the affected rat joint. These findings support the practice of tribosupplementation with lubricin for retarding cartilage degeneration and possibly the development of posttraumatic osteoarthritis.

Atelocollagen Injections Improve Outcomes in the Nonsurgical Treatment of Grade III Medial Collateral Ligament Injuries.

Background: The purpose of this study was to evaluate the clinical outcomes of atelocollagen injections in isolated grade III medial collateral ligament (MCL) injuries of the knee joint. Methods: A total of 50 participants were included in this retrospective study. Twenty-six patients underwent conservative treatment with a single atelocollagen injection, while the remaining patients underwent only typical conservative treatment. All participants underwent magnetic resonance imaging to identify and grade MCL injury. Valgus stress radiography was performed on both knees at 6 and 12 months after the injury. The visual analog scale (VAS) score was collected at the first visit and at 2 weeks, 6 weeks, 6 months, and 12 months after injury. The International Knee Documentation Committee (IKDC) formula activity level and Lysholm score were evaluated for patient-reported outcomes at the first visit and at 6 and 12 months after injury. The participant's return to the pre-injury activity level ratio was measured by comparing the IKDC formula activity level at 12 months after the injury with that before the injury. Results: The VAS and Lysholm scores improved over time in both groups. The VAS and Lysholm scores were significantly better in the collagen injection group than in the control group. Regarding the activity level, the collagen injection group showed significantly better results at the 6-month follow-up, but there was no significant difference at the 12-month follow-up. The medial gap in the injured knee and the side-to-side difference (SSD) in both groups gradually decreased over time. The SSD in the collagen injection group was significantly smaller than that in the control group. Conclusions: Atelocollagen injections resulted in better clinical and radiologic outcomes along with a higher rate of return to the pre-injury activity level, thereby exhibiting a positive effect in the nonsurgical treatment of grade III MCL injuries.

Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254).

OBJECTIVE: To evaluate the clinical effectiveness of intraarticular IL-1 receptor antagonist (IL-1Ra) for anterior cruciate ligament (ACL) tear. METHODS: Eleven patients with acute ACL tear confirmed by magnetic resonance imaging (MRI) were randomized to receive a single intraarticular injection of IL-1Ra (anakinra 150 mg, n = 6) or equal volume of saline placebo (1 ml, n = 5). The double-blinded treatment was administered a mean 2 weeks after injury. Synovial fluid (SF) (n = 9 patients) and sera (all patients) were available at baseline (prior to injection) and immediately prior to surgery (mean 35 days later) and analyzed for SF IL-1α, IL-1ß, IL-1Ra and serum hyaluronan (HA), an indicator of synovial inflammation. The primary outcome, standardized Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, was obtained at 0 (baseline), 4, and 14 days after injection. RESULTS: Compared with placebo, the IL-1Ra group had substantially greater improvement in key outcomes over 14 days (KOOS pain P = 0.001; activities of daily living P = 0.0015; KOOS sports function P = 0.0026; KOOS quality of life (QOL) P = 0.0048; and total KOOS P < 0.0001). There were no adverse reactions in either group. SF IL-1α (P = 0.05) and serum HA (P = 0.03), but not IL-1ß, or IL-1Ra, decreased significantly in the IL-1Ra but not the placebo treated patients. Compared with placebo, IL-1α was borderline significantly different in the IL-1Ra treated group (P = 0.06). CONCLUSIONS: Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval. This promising proof of concept study provides a new paradigm for studies of acute joint injury and suggests that a larger follow-up study is warranted.

Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration.

PURPOSE: Osteochondral defects (i.e., defects which affect both the articular cartilage and underlying subchondral bone) are often associated with mechanical instability of the joint and therefore with the risk of inducing osteoarthritic degenerative changes. This review addresses the current surgical treatments and most promising tissue engineering approaches for articular cartilage and subchondral bone regeneration. METHODS: The capability to repair osteochondral or bone defects remains a challenging goal for surgeons and researchers. So far, most clinical approaches have been shown to have limited capacity to treat severe lesions. Current surgical repair strategies vary according to the nature and size of the lesion and the preference of the operating surgeon. Tissue engineering has emerged as a promising alternative strategy that essentially develops viable substitutes capable of repairing or regenerating the functions of damaged tissue. RESULTS: An overview of novel and most promising osteochondroconductive scaffolds, osteochondroinductive signals, osteochondrogenic precursor cells, and scaffold fixation approaches are presented addressing advantages, drawbacks, and future prospectives for osteochondral regenerative medicine. CONCLUSION: Tissue engineering has emerged as an excellent approach for the repair and regeneration of damaged tissue, with the potential to circumvent all the limitations of autologous and allogeneic tissue repair. LEVEL OF EVIDENCE: Systematic review, Level III.

Hyaluronan injection therapy for athletic patients with patellar tendinopathy.

BACKGROUND: Patellar tendinopathy produces activity-related pain and focal tenderness at the attachment of the patellar tendon at the lower pole of the patella. It frequently causes a reduction in athletic ability. An injection of hyaluronan was found to be useful for patellar tendinopathy, provided the indication is appropriate, based on the authors' pilot cases. The purpose of this study was to summarize the clinical experience of and to describe the appropriate indication for this injection therapy. METHODS: Fifty patients were treated from January 1999 to December 2006. The observation period averaged 25.7 months (range 6-88). All patients were graded stage 2 or 3 by Blazina's classification. Each treatment was counted separately for 9 patients (10 knees) who had more than one treatment period with 3 months or more between the injections. There were 4 bilaterally injected patients. Patellar tendinopathy was classified into 4 types according to the degree of tenderness and the regions that are tender. Hyaluronan was injected into the interface between the patellar tendon and the infrapatellar fat pad at the proximal insertion, or into the region of maximum tenderness. RESULTS: The total number of injections was 135, and there were an average of 2.0 injections per case (range 1-11). Following treatment, 54 % of the cases were rated in excellent condition, as they were able to return to their previous athletic activities with little difficulty, while 40 % of the cases were rated in good condition-these patients were able to return to their previous sporting activities with some degree of limitation. CONCLUSIONS: Hyaluronan injection therapy for athletic patients with patellar tendinopathy is an optional but effective treatment.

Acceptability of a nurse-led non-pharmacological complex intervention for knee pain: Nurse and patient views and experiences.

OBJECTIVES: The overall purpose of this research programme is to develop and test the feasibility of a complex intervention for knee pain delivered by a nurse, and comprising both non-pharmacological and pharmacological interventions. In this first phase, we examined the acceptability of the non-pharmacological component of the intervention; issues faced in delivery, and resolved possible challenges to delivery. METHODS: Eighteen adults with chronic knee pain were recruited from the community. The intervention comprised holistic assessment, education, exercise, weight-loss advice (where appropriate) and advice on adjunctive treatments such as hot/cold treatments, footwear modification and walking aids. After nurse training, the intervention was delivered in four sessions spread over five weeks. Participants had one to one semi-structured interview at the end of the intervention. The nurse was interviewed after the last visit of the last participant. These were audio recorded and transcribed verbatim. Themes were identified by one author through framework analysis of the transcripts, and cross-checked by another. RESULTS: Most participants found the advice from the nurse easy to follow and were satisfied with the package, though some felt that too much information was provided too soon. The intervention changed their perception of managing knee pain, learning that it can be improved with self-management. However, participants thought that the most challenging part of the intervention was fitting the exercise regime into their daily routine. The nurse found discussion of goal setting to be challenging. CONCLUSION: The nurse-led package of care is acceptable within a research setting. The results are promising and will be applied in a feasibility randomised-controlled trial.

Anatomical description and short-term follow up clinical results for ultrasound-guided injection of medial collateral ligament bursa: New conservative treatment option for symptomatic degenerative medial meniscus tear.

BACKGROUND: In this study, we investigated newly developed ultrasound (US)-guided medial collateral ligament (MCL) bursa injection as a conservative therapy for symptomatic degenerative medial meniscal (MM) tears. We aimed to describe the anatomical target and precise technique of this injection, confirm its accuracy using fresh cadaveric knees, and then evaluate preliminary clinical outcomes. METHODS: Anatomical studies were performed on three fresh cadavers. For the clinical study, 50 patients with medial knee joint pain without knee osteoarthritis were treated with US-guided MCL bursa injection. Severity of pain was assessed pre-injection, and 1 week and 4 weeks post-injection using a 0-10 numerical rating scale (NRS). Clinical success was defined as a full return to daily activities. All patients underwent magnetic resonance imaging (MRI) within 1 week of the first injection. Patients who underwent surgery within 12 months of the first injection were investigated as clinically unsuccessful cases, and MRI and arthroscopic findings were examined. RESULTS: Compared with pre-injection (6.8 ±â€¯1.2), the average NRS score was significantly lower at 1 week (1.8 ±â€¯2.0) and at 4 weeks (1.5 ±â€¯1.7) post-injection (both P < 0.01). The primary clinical success rate was 76.0%, and injection-related adverse events were not observed. Nine patients underwent surgery (arthroscopic surgery for degenerative flap tear (n = 7) and high tibial osteotomy for medial meniscus posterior root tear and proximal tibial malalignment (n = 2)). CONCLUSIONS: US-guided MCL bursa injection is safe, reproducible, and effective for symptomatic MM degenerative tears. However, US-guided injections of the MCL bursa may be ineffective for flap tears and posterior root tears.

In vitro inhibition of compression-induced catabolic gene expression in meniscal explants following treatment with IL-1 receptor antagonist.

BACKGROUND: Damage to the knee meniscus may result in tears that are difficult or unable to heal, and are often treated by partial removal of the damaged tissue. In vitro, 20% dynamic compressive strains on meniscal tissue explants have resulted in an increase in the release of sulfated glycosaminoglycans (GAG) and nitric oxide (NO) from the tissue explants and increased expression of matrix metalloproteinases (MMP) and interleukin-1α (IL-1α). The objective of this study was to explore the efficacy of IL-1 blockade on the expression of a wide range of genes, as well as NO and GAG release, following dynamic compression of porcine meniscal explants. METHODS: Explants were dynamically compressed for 2 h at 1 Hz to 0, 10, or 20% strain with and without a pre-treatment of 500 ng/ml interleukin-1 receptor antagonist (IL-1RA). Relative changes in gene expression of IL-1α, MMP-1, -3, -13, A Disintegrin and Metalloproteinase with ThromboSpondin 4 (ADAMTS-4), ADAMTS-5, iNOS, aggrecan, and COX-2, as well as changes in NO and GAG release, were measured with standard biochemical assays. RESULTS: Expression of IL-1α, MMP-3, MMP-13, and ADAMTS-4 in superficial explants was significantly downregulated at 20% dynamic strain compared to 10% strain following treatment with IL-1RA. GAG and NO release were not significantly influenced by IL-1RA treatment. CONCLUSIONS: Treatment of meniscal explants with IL-1RA inhibited the expression of many catabolic genes following a single bout of high dynamic strain. IL-1RA may therefore be a potential therapy option during the acute phase of meniscal tear or meniscectomy treatment.

Intra-articular hyaluronic acid: potential treatment of younger patients with knee injury and/or post-traumatic arthritis.

Anterior cruciate ligament (ACL) and meniscal injuries are common in both athletes and the general population. Such injuries may lead to early-onset post-traumatic osteoarthritis (OA) in 50% to 60% of patients, regardless of whether patients had reconstruction performed. In younger patients, intra-articular (IA) injection of hyaluronic acid (HA) may be useful for improving short-term outcomes and possibly slowing or arresting the progression of OA. Hyaluronic acid has anti-inflammatory, anabolic, and chondroprotective effects, which have been demonstrated in in vitro and animal models of meniscal and ACL injury. Results from several clinical trials and patient series have demonstrated the benefit of IA HA injection in younger patients with acute knee damage, including symptomatic meniscal tears and isolated ACL injury with chondral injury, although evidence for this is less extensive than the large database supporting the use of IA HA injection in older patients with knee OA. Administration of HA has been shown to improve outcomes in patients undergoing knee arthroscopy, and IA HA also has direct antinociceptive effects that may contribute to its benefit in patients with patellofemoral pain. However, the use of IA HA in patients with ACL injury or early OA has been evaluated in only a few studies. Thus, there is a need for larger-scale randomized controlled trials with longer durations of follow-up to provide more definitive evaluation of the efficacy and safety of IA HA in these patients. Such studies provide an opportunity to further elucidate the benefits of IA HA in younger patients with knee damage and may result in appropriate expansion of use in this large population, which has a substantial need for new treatment alternatives.

Analgesic and anti-inflammatory articular effects of essential oil and camphor isolated from Ocimum kilimandscharicum Gürke leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain. AIM OF STUDY: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice. MATERIAL AND METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 µg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP. CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.

Repair of osteochondral defect using icariin-conditioned serum combined with chitosan in rabbit knees.

BACKGROUND: Osteochondral defects caused by an acute traumatic injury or articular degeneration remains difficult to be manipulated. Repair of articular defects is still a great challenge for both tissue engineers and orthopedic surgeons. Therefore, combination of biomaterials with cartilage promotive drugs is well worth being developed to support the regeneration of both cartilage and subchondral bone. METHODS: Rabbits undergoing osteochondral defect surgery were intrarticularly injected with icariin-conditioned serum (ICS), chitosan (CSSH) and combination of ICS with CSSH, respectively. Gait analysis was performed using VICON motion capture system. ICRS score and immunohistochemical (IHC) analysis including H&E, Safranin O, toluidine blue and collagen II staining was employed to evaluate macroscopic cartilage regeneration and determine the morphologic repair of cartilage. RESULTS: Rabbits with the treatment of ICS or CSSH alone showed mild improvement in hopping time and range of joint angles while ICS-CSSH group exhibited longer jumping time and larger range of joint angles. In addition, femoral condyle in ICS-CSSH rabbits could be seen with more native cartilage and subchondral bone regeneration in both macroscopic observation and IHC analysis. CONCLUSION: ICS combined with CSSH could promote the repair of osteochondral defect in rabbit knees. Combination of biomaterials with cartilage promotive drugs may ultimately have profound implications in the management of cartilage defect.