Effect of Demineralized Bone Matrix, Bone Marrow Mesenchymal Stromal Cells, and Platelet-Rich Plasma on Bone Tunnel Healing After Anterior Cruciate Ligament Reconstruction: A Comparative Micro-Computed Tomography Study in a Tendon Allograft Sheep Model.

BACKGROUND: The effect of demineralized bone matrix (DBM), bone marrow-derived mesenchymal stromal cells (BMSCs), and platelet-rich plasma (PRP) on bone tunnel healing in anterior cruciate ligament reconstruction (ACLR) has not been comparatively assessed. HYPOTHESIS: These orthobiologics would reduce tunnel widening, and the effects on tunnel diameter would be correlated with tunnel wall sclerosis. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 sheep underwent unilateral ACLR using tendon allograft and outside-in interference screw fixation. The animals were randomized into 4 groups (n = 5 per group): Group 1 received 4mL of DBM paste, group 2 received 10 million BMSCs in fibrin sealant, group 3 received 12 mL of activated leukocyte-poor platelet-rich plasma, and group 4 (control) received no treatment. The sheep were euthanized after 12 weeks, and micro-computed tomography scans were performed. The femoral and tibial tunnels were divided into thirds (aperture, midportion, and exit), and the trabecular bone structure, bone mineral density (BMD), and tunnel diameter were measured. Tunnel sclerosis was defined by a higher bone volume in a 250-µm volume of interest compared with a 4-mm volume of interest surrounding the tunnel. RESULTS: Compared with the controls, the DBM group had a significantly higher bone volume fraction (bone volume/total volume [BV/TV]) (52.7% vs 31.8%; P = .020) and BMD (0.55 vs 0.47 g/cm3; P = .008) at the femoral aperture and significantly higher BV/TV at femoral midportion (44.2% vs 32.9%; P = .038). There were no significant differences between the PRP and BMSC groups versus controls in terms of trabecular bone analysis or BMD. In the controls, widening at the femoral tunnel aperture was significantly greater than at the midportion (46.7 vs 41.7 mm2; P = .034). Sclerosis of the tunnel was common and most often seen at the femoral aperture. In the midportion of the femoral tunnel, BV/TV (r = 0.52; P = .019) and trabecular number (r S = 0.50; P = .024) were positively correlated with tunnel widening. CONCLUSION: Only DBM led to a significant increase in bone volume, which was seen in the femoral tunnel aperture and midportion. No treatment significantly reduced bone tunnel widening. Tunnel sclerosis in the femoral tunnel midportion was correlated significantly with tunnel widening. CLINICAL RELEVANCE: DBM might have potential clinical use to enhance healing in the femoral tunnel after ACLR.

Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction.

PURPOSE: The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). METHODS: Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal-noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon-bone healing, respectively. Spearman's rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. RESULTS: The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = - 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. CONCLUSIONS: BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI.

Characterisation of the tensile properties of Demineralised Cortical Bone when used as an anterior cruciate ligament allograft.

BACKGROUND: Graft choice in anterior cruciate ligament (ACL) reconstruction remains controversial and some grafts fail due to inadequate osteointegration. Demineralised cortical bone (DCB) is an osteoinductive collagen-based scaffold. The aim of this study was to measure the tensile properties of DCB from different locations and from different ages, and determine its compatibility with current ACL fixation systems. METHODS: The tensile properties of DCB manufactured from femur and tibia of young (9 month) and old (2-3 years) sheep was measured to determine the most appropriate graft choice. The ultimate load and stiffness of DCB allograft using two fixation systems, interference screws and sutures tied around screw posts, was measured ex vivo in an ovine ACL reconstruction model. Comparison was made with superficial digital flexor tendon (SDFT) and ovine ACL. RESULTS: DCB derived from young tibia had the highest ultimate load and stiffness of 67.7 ± 10.6 N and 130.2 ± 64.3 N/mm respectively. No DCB fixation system reached the published peak in vivo force through the ovine ACL of 150 N. SDFT fixation with interference screws (308.2 ± 87.3 N) did reach the in vivo threshold but was significantly weaker than ovine ACL (871.0 ± 64.2 N). CONCLUSION: The tensile properties of DCB were influenced by the donor age and bone. Owing to inferior tensile properties and incompatibility with suspensory fixation devices, this study indicates DCB is inferior to current tendon grafts options for ACL reconstruction.

Decellularized porcine xenograft for anterior cruciate ligament reconstruction: A histological study in sheep comparing cross-pin and cortical suspensory femoral fixation.

AIMS: To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements. METHODS: A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization). RESULTS: The pSFT remodelled into a ligament-like structure and no adverse inflammatory reaction was seen. The ground reaction force in the operated leg of the Endobutton group was higher at 11 weeks (p < 0.05). An indirect insertion was seen at the graft-bone interface characterized by Sharpey-like fibres. Qualitative differences in tendon remodelling were seen between the two groups, with greater crimp-like organization and more aligned collagen fibres seen with Endobutton fixation. One graft rupture occurred in the cross-pin group, which histologically showed low collagen organization. CONCLUSION: Decellularized pSFT xenograft remodels into a ligament-like structure after 12 weeks and regenerates an indirect-type insertion with Sharpey-like fibres. No adverse inflammatory reaction was observed. Cortical suspensory femoral fixation was associated with more enhanced graft remodelling and earlier functional recovery when compared with the stiffer cross-pin fixation.

Factors that influence medical student learning in the operating room.

Introduction: The operating room (OR) is a dynamic, high-pressure clinical setting that offers a unique workplace-based learning environment for students. We undertook a narrative synthesis of the literature to identify factors that influence medical student learning in the OR, and we recommend educational strategies that maximize "theater-based learning". Methods: Key words were searched across three databases PubMed, EMBASE and ERIC (Education Resource Information Center). Eligible studies included original articles published after 1997 presenting empirical research on factors that influence medical students learning in the OR. Methodological quality was measured using the Newcastle-Ottawa Score for education. Results: We identified 764 studies on the topic of student learning in the OR, of which 16 studies fulfilled inclusion criteria. The quality assessments demonstrated a mean value of 2.1 out of a maximum of 6. Conclusions: We identified five key domains that influence student learning in the OR: emotional factors, socio-environmental factors, organizational factors, factors related to educational relevance and factors related to the educator. Educational strategies to enhance theater-based learning include: an induction and physical orientation, clear learning objectives, educator feedback, and simulation.

Demineralized Bone Matrix to Augment Tendon-Bone Healing: A Systematic Review.

BACKGROUND: Following injury to the rotator cuff and anterior cruciate ligament, a direct enthesis is not regenerated, and healing occurs with biomechanically inferior fibrous tissue. Demineralized bone matrix (DBM) is a collagen scaffold that contains growth factors and is a promising biological material for tendon and ligament repair because it can regenerate a direct fibrocartilaginous insertion via endochondral ossification. PURPOSE: To provide a comprehensive review of the literature investigating the use of DBM to augment tendon-bone healing in tendon repair and anterior cruciate ligament reconstruction (ACLR). STUDY DESIGN: Systematic review. METHODS: Electronic databases (MEDLINE and EMBASE) were searched for preclinical and clinical studies that evaluated the use of DBM in tendon repair and ACLR. Search terms included the following: ("demineralized bone matrix" OR "demineralized cortical bone") AND ("tissue scaffold" OR "tissue engineering" OR "ligament" OR "tendon" OR "anterior cruciate ligament" OR "rotator cuff"). Peer-reviewed articles written in English were included, and no date restriction was applied (searches performed February 10, 2017). Methodological quality was assessed with peer-reviewed scoring criteria. RESULTS: The search strategy identified 339 articles. After removal of duplicates and screening according to inclusion criteria, 8 studies were included for full review (tendon repair, n = 4; ACLR, n = 4). No human clinical studies were identified. All 8 studies were preclinical animal studies with good methodological quality. Five studies compared DBM augmentation with non-DBM controls, of which 4 (80%) reported positive findings in terms of histological and biomechanical outcomes. CONCLUSION: Preclinical evidence indicates that DBM can improve tendon-bone healing, although clinical studies are lacking. A range of animal models of tendon repair and ACLR showed that DBM can re-create a direct fibrocartilaginous enthesis, although the animal models are not without limitations. Before clinical trials are justified, research is required that determines the best source of DBM (allogenic vs xenogenic) and the best form of DBM (demineralized cortical bone vs DBM paste) to be used in them.

Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients.

BACKGROUND: Neurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype-phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown. METHODS: We evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan-Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2. RESULTS: The study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6-15 had lower mortality than patients with splice-site mutations in exons 1-5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier. CONCLUSIONS: Continuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.

Severe Acute Subdural Hematoma in a Child following a Minor Head Trauma in the Context of a Recent Antecedent Head Injury: A Case Report.

Knowledge of the force required to generate a subdural hematoma is important when considering the veracity of histories given by family members of young children. Traditional wisdom is that a substantial impact is required to cause an acute subdural hematoma. We present a case of acute subdural hematoma following a low-level fall in a 3-year-old patient. An antecedent head injury associated with normal CT scan might have had some bearing on this outcome.

Management of glenohumeral synovitis secondary to influenza vaccination.

Glenohumeral synovitis is a rare complication of vaccination that can lead to shoulder dysfunction and prolonged pain. We report a case of florid glenohumeral synovitis after routine influenza vaccination, which we consider to have occurred because of the unintentional injection of antigenic material into synovial tissues, resulting in an immune-mediated inflammatory reaction. We provide a review of the literature for this condition and describe an invasive management approach, providing, for the first time, an arthroscopic evaluation and histopathological analysis.

Component size mismatch of metal on metal hip arthroplasty: an avoidable never event.

Size mismatch of components used in total hip arthroplasty is a serious, preventable patient safety incident of unknown prevalence as many cases are not detected. Component size mismatch was found in 11 cases (0.9%) at our retrieval centre. All cases of mismatch were not detected on plain radiograph during routine clinical follow up and blood metal ion levels were elevated above the MHRA action level of 7 ppb. Root cause analysis identified manufacturer, hospital and surgeon factors that need to be addressed to reduce the incidence of this avoidable clinical problem. Retrieval analysis is the only method of confirming size mismatch and is likely to be under-represented in National Joint Registries that record the indication for revision at the time of revision.