Treatment of post-meniscectomy knee symptoms with medial meniscus replacement results in greater pain reduction and functional improvement than non-surgical care.

PURPOSE: Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6-25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. METHODS: In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. RESULTS: Treated subjects had a median age of 52 years old (range 30-69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5-430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). CONCLUSION: Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. LEVEL OF EVIDENCE: I.

Preliminary Results From a US Clinical Trial of a Novel Synthetic Polymer Meniscal Implant.

BACKGROUND: At least 760,000 outpatient meniscectomies are performed in the United States each year, making this the most common musculoskeletal procedure. However, meniscal resection can alter the joint biomechanics and overload the articular cartilage, which may contribute to degenerative changes and the need for knee replacement. Avoiding or delaying knee replacement is particularly important in younger or more active patients. Synthetic meniscal implants have been developed in an attempt to restore the natural joint biomechanics, alleviate pain and disability, and potentially minimize degenerative changes in patients who require meniscectomy. PURPOSE: To evaluate the preliminary results from 2 ongoing trials that are evaluating the safety and effectiveness of a synthetic polymer meniscal implant (NUsurface; Active Implants, LLC). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This was a preliminary analysis of the first 100 patients enrolled across 2 studies for 12 months: a single-arm, intervention-only study and a randomized controlled trial comparing the investigational meniscal implant with nonsurgical therapy. There were 65 patients in the implant group (30 randomized) and 35 in the control group. Outcomes included Knee injury and Osteoarthritis Outcome Score (KOOS) and adverse events (AEs) collected at baseline and follow-up visits of 6 weeks, 6 months, and 12 months. RESULTS: No statistically significant differences were found in baseline characteristics between the implant and control groups. At 12 months, follow-up KOOS data were available for 87% of the 100 included patients. Significantly greater improvements from baseline were observed in the implant group compared with controls in all KOOS subcomponents, except for symptoms (119%-177% greater improvement at 12 months). AEs were reported at similar rates between the 2 groups, with 12 AEs among 11 patients in the implant group (16.9%) versus 5 AEs among 5 patients (14.3%) in the control group (P = .99). CONCLUSION: These preliminary results suggest significant improvements in pain and function scores with the implant over nonsurgical therapy and a similar adverse event rate.

Bilateral distal tibial transitional ankle fractures.

A 13-year-old boy presented to the emergency department with bilateral ankle pain and swelling following a 5-foot fall from a swing set.

MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature.

1. 3,4-Methylenedioxymethamphetamine (MDMA or 'ecstasy') decreases the 5-HT concentration, [3H]-paroxetine binding and tryptophan hydroxylase activity in rat forebrain, which has been interpreted as indicating 5-HT neurodegeneration. This has been questioned, particularly the 5-HT loss, as MDMA can also inhibit tryptophan hydroxylase. We have now evaluated the validity of these parameters as a reflection of neurotoxicity. 2. Male DA rats were administered MDMA (12.5 mg kg(-1), i.p.) and killed up to 32 weeks later. 5-HT content and [3H]-paroxetine binding were measured in the cortex, hippocampus and striatum. Parallel groups of treated animals were administered NSD-1015 for determination of in vivo tryptophan hydroxylase activity and 5-HT turnover rate constant. 3. Tissue 5-HT content and [3H]-paroxetine binding were reduced in the cortex (26-53%) and hippocampus (25-74%) at all time points (1, 2, 4, 8 and 32 weeks). Hydroxylase activity was similarly reduced up to 8 weeks, but had recovered at 32 weeks. The striatal 5-HT concentration and [3H]-paroxetine binding recovered by week 4 and hydroxylase activity after week 1. In all regions, the reduction in 5-HT concentration did not result in an altered 5-HT synthesis rate constant. 4. Administering MDMA to animals when housed at 4 degrees C prevented the reduction in [3H]-paroxetine binding and hydroxylase activity observed in rats housed at 22 degrees C, but not the reduction in 5-HT concentration. 5. These data indicate that MDMA produces long-term damage to serotoninergic neurones, but this does not produce a compensatory increase in 5-HT synthesis in remaining terminals. It also highlights the fact that measurement of tissue 5-HT concentration may overestimate neurotoxic damage.

A comparative study on the acute and long-term effects of MDMA and 3,4-dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice.

1. This study investigated whether the immediate and long-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in mouse brain are due to the parent compound and the possible contribution of a major reactive metabolite, 3,4-dihydroxymethamphetamine (HHMA), to these changes. The acute effect of each compound on rectal temperature was also determined. 2. MDMA given i.p. (30 mg kg(-1), three times at 3-h intervals), but not into the striatum (1, 10 and 100 microg, three times at 3-h intervals), produced a reduction in striatal dopamine content and modest 5-HT reduction 1 h after the last dose. MDMA does not therefore appear to be responsible for the acute monoamine release that follows its peripheral injection. 3. HHMA does not contribute to the acute MDMA-induced dopamine depletion as the acute central effects of MDMA and HHMA differed following i.p. injection. Both compounds induced hyperthermia, confirming that the acute dopamine depletion is not responsible for the temperature changes. 4. Peripheral administration of MDMA produced dopamine depletion 7 days later. Intrastriatal MDMA administration only produced a long-term loss of dopamine at much higher concentrations than those reached after the i.p. dose and therefore bears little relevance to the neurotoxicity. This indicates that the long-term effect is not attributable to the parent compound. HHMA also appeared not to be responsible as i.p. administration failed to alter the striatal dopamine concentration 7 days later. 5. HHMA was detected in plasma, but not in brain, following MDMA (i.p.), but it can cross the blood-brain barrier as it was detected in the brain following its peripheral injection. 6. The fact that the acute changes induced by i.p. or intrastriatal HHMA administration differed indicates that HHMA is metabolised to other compounds which are responsible for changes observed after i.p. administration.