Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis.

Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24 h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration. Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6 weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes. Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24 h or 3 weeks post-surgery (n = 5-7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage. Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24 h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham. Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections.

Oxacillin plus ertapenem combination therapy leads to rapid blood culture clearance and positive outcomes among patients with persistent MSSA bacteraemia: a case series.

BACKGROUND: Bloodstream infections caused by MSSA are associated with significant morbidity and mortality. Traditional treatment of MSSA bacteraemia includes an IV antistaphylococcal ß-lactam and surgical source control when indicated. OBJECTIVES: To evaluate the time to blood culture clearance as well as in-hospital and 90 day mortality in patients with persistent MSSA bacteraemia treated with combination antistaphylococcal penicillin plus carbapenem therapy. METHODS: Consecutive patients with persistent MSSA bacteraemia treated with combination therapy were identified by study investigators and reviewed by independent clinicians. The decision to initiate combination therapy was made by the consulting clinician or by the institution's multidisciplinary endocarditis team. RESULTS: Among 10 patients with a median of 5 days of persistent MSSA bacteraemia, treatment with an antistaphylococcal penicillin plus carbapenem led to sterilization of blood cultures in all patients. Blood culture clearance occurred in a median of 1 day and patients received a median of 6 days of combination treatment. Four of seven patients who underwent source control of their primary site of infection cleared their bacteraemia on combination therapy prior to the surgical intervention. All patients survived to hospital discharge and 90 days post-discharge. CONCLUSIONS: These data extend prior findings and provide further evidence that suggests the potential benefits of combination therapy among patients with persistent MSSA bacteraemia.

Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development.

INTRODUCTION: Micronized dehydrated human amnion/chorion membrane (µ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of µ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of µ-dHACM would attenuate OA progression. METHODS: Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. Twenty four hours post-surgery, µ-dHACM or saline was injected intra-articularly into the rat joint. Naïve rats also received µ-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-µCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery. RESULTS: There was no measured baseline effect of µ-dHACM on cartilage in naïve animals. Histological staining of treated joints showed presence of µ-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with µ-dHACM. EPIC-µCT analysis quantitatively showed that µ-dHACM reduced proteoglycan loss in MMT animals. CONCLUSIONS: µ-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of µ-dHACM may have a therapeutic effect on OA development.