Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol.

INTRODUCTION: Fracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed. METHODS AND ANALYSIS: A multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring. ETHICS AND DISSEMINATION: Participant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356-2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER: NCT02999022.

Photodynamic Therapy for the Treatment of Vertebral Metastases: A Phase I Clinical Trial.

PURPOSE: Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA). PATIENTS AND METHODS: This first-in-human trial used a single 6 mg/m2 dose of the clinical photosensitizer Visudyne with escalating laser light doses. Following a cohort of light-only controls (n = 6), the drug and light treatment groups (n = 6 each) were 50, 100, 150, and 200 J/cm. VCA was performed within 15 minutes following PDT. Patients were clinically reviewed at 1 and 6 weeks. The primary outcome measure was safety from a neurologic perspective. RESULTS: Thirty patients comprising a variety of primary tumors were treated with PDT and either KP or VP. Vertebral PDT was technically feasible and delivered in all study patients. No dose groups showed significant increases in pain as defined by the generic SF-36 as well as disease-specific EORTC-QLQ-BM22 and EORTC-QLQ-C15-PAL questionnaires. The 50 and 100 J/cm groups showed the most significant pain reduction (P < 0.05). Twelve (40%) patients experienced complications during the study including 3 patients with further vertebral fracture progression by 6 weeks despite VCA. No complications were directly attributed to PDT. CONCLUSIONS: Using the parameters described, vertebral PDT as an adjunct to VCA is safe from a pharmaceutical and neurologic perspective. The results of this trial motivate scale-up study evaluating potential PDT efficacy in vertebral metastatic treatment.

Perceived personal importance of exercise and fears of re-injury: a longitudinal study of psychological factors related to activity after anterior cruciate ligament reconstruction.

BACKGROUND: Psychological perceptions are increasingly being recognized as important to recovery and rehabilitation post-surgery. This research longitudinally examined perceptions of the personal importance of exercise and fears of re-injury over a three-year period post anterior cruciate ligament (ACL) reconstruction. Stability and change in psychological perceptions was examined, as well as the association of perceptions with time spent in different types of physical activity, including walking, household activities, and lower and higher risk for knee injury activities. METHODS: Participants were athletes, 18-40 years old, who underwent ACL reconstruction for first-time ACL injuries. They were recruited from a tertiary care centre in Toronto, Canada. Participants completed interviewer-administered questionnaires pre-surgery and at years one, two and three, postoperatively. Questions assessed demographics, pain, functional limitations, perceived personal importance of exercise, fear of re-injury and physical activities (i.e., walking; household activities; lower risk for knee injury activities; higher risk for knee injury activities). Analyses included fixed-effect longitudinal modeling to examine the association of a fear of re-injury and perceived personal importance of exercise and changes in these perceptions with the total hours spent in the different categories of physical activities, controlling for other factors. RESULTS: Baseline participants were 77 men and 44 women (mean age = 27.6 years; SD = 6.2). At year three, 78.5% of participants remained in the study with complete data. Fears of re-injury decreased over time while personal importance of exercise remained relatively stable. Time spent in walking and household activities did not significantly change with ACL injury or surgery. Time spent in lower and higher risk of knee injury physical activity did not return to pre-injury levels at three years, post-surgery. Greater time spent in higher risk of knee injury activities was predicted by decreases in fears of re-injury and by greater personal importance of exercise. CONCLUSIONS: This study highlights not only fears of re-injury, which has been documented in previous studies, but also the perceived personal importance of exercise in predicting activity levels following ACL reconstructive surgery. The findings can help in developing interventions to aid individuals make decisions about physical activities post knee injury and surgery.

Anterior cruciate ligament reconstruction by using bioabsorbable femoral cross pins: MR imaging findings at follow-up and comparison with clinical findings.

PURPOSE: To determine the frequency of imaging findings and complications related to bioabsorbable femoral cross pins at follow-up magnetic resonance (MR) imaging studies after anterior cruciate ligament (ACL) reconstruction and compare these MR imaging findings with clinical evaluation findings. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and informed consent was waived. Follow-up MR imaging studies (average, 26 months after surgery) in 218 patients with prior ACL reconstruction were retrospectively reviewed. Cross-pin fracture, posterior transcortical breach, migration, resorption, and lateral prominence of cross pins, as well as the cross-pin angle relative to the transepicondylar line, were investigated on MR images. The clinical evaluation included Lachman, anterior drawer, and pivot shift tests, as well as assessment for joint tenderness. RESULTS: Fracture, posterior transcortical breach, migration, and lateral prominence of cross pins were excluded from analysis when at least one cross pin was completely resorbed (n = 16 patients). Forty-five fractured cross pins were seen in 35 (17%) of 202 patients. The posterior femoral cortex was breached in 57 (28%) of 202 patients. Migration of fractured pin fragments occurred in 12 (6%) of 202 patients. There was a significant relationship between fractures and posterior breach of cross pins (P = .001), as well as between cross-pin angles and fractures (P = .002). Both cross pins were completely resorbed in 12 (6%) of 218 patients (average time since surgery, 53 months; range, 8-92 months). No significant association was found between any MR imaging finding related to cross pins and clinical test findings. CONCLUSION: Fracture and posterior transcortical breach of bioabsorbable femoral cross pins, commonly seen at follow-up MR imaging studies, do not correlate with clinical findings of joint instability or pain. Posteriorly angulated cross pins and posterior transcortical breach are significantly associated with cross-pin fractures.

Anterior cruciate ligament reconstruction grafts: MR imaging features at long-term follow-up--correlation with functional and clinical evaluation.

PURPOSE: To assess the presence of increased intrasubstance signal intensity within anterior cruciate ligament (ACL) grafts and to assess whether such signal intensity changes are correlated to clinical assessments of graft instability and patient function 4-12 years after ACL reconstruction. MATERIALS AND METHODS: Ethical permission and written informed patient consent were obtained. The study was HIPAA compliant. Forty-seven patients were included and underwent 1.5-T magnetic resonance (MR) imaging of the knee that was treated surgically. Signal intensity characteristics of the ACL graft were evaluated on sagittal intermediate-weighted and sagittal and axial T2-weighted fast spin-echo MR images. The amount of signal intensity change, femoral and tibial graft tunnel position, and orientation of ACL graft in the coronal plane were assessed. Objective index of graft stability or laxity was performed with arthrometric testing, and subjective function was assessed by using International Knee Documentation Committee (IKDC) scoring. RESULTS: Increased intrasubstance graft signal intensity was found in 70 % (33 of 47) and in 64% (30 of 47) of patients on intermediate-weighted MR images and T2-weighted MR images, respectively. When present, intrasubstance graft signal intensity changes involved less than 25% of the maximal cross-sectional area of the graft in 70% (23 of 33) of cases on intermediate-weighted acquisitions and in 70% (21 of 30) of cases on T2-weighted acquisitions. No significant association was seen between graft signal intensity changes on intermediate-weighted and T2-weighted images and IKDC score (P = .667 and .698, respectively), arthrometric testing (P = .045-.99), and time since surgery (P = .592 and .610, respectively). CONCLUSION: Small amounts of increased intrasubstance graft signal intensity on intermediate- and T2-weighted images can be seen after ACL reconstruction at long-term follow-up of 4 years or longer and do not necessarily correlate with findings of joint instability or functional limitations in patients after ACL repair.