Validation of quantitative magnetic resonance imaging-based apparent bone volume fraction in peri-articular tibial bone of cadaveric knees.

BACKGROUND: In the knee, high-resolution magnetic resonance (MR) imaging has demonstrated that increased apparent bone volume fraction (trabecular bone volume per total volume; BV/TV) in the peri-articular proximal medial tibia is associated with joint space narrowing and the presence of bone marrow lesions. However, despite evidence of construct validity, MR-based apparent BV/TV has not yet been cross-validated in the proximal medial tibia by comparison with a gold standard (e.g., micro-computed tomography [microCT]). In this cadaveric validation study we explored the association between MR-based apparent BV/TV and microCT-based BV/TV in the proximal peri-articular medial tibia. METHODS: Fresh cadaveric whole knee specimens were obtained from individuals 51 to 80 years of age with no knee pathology other than osteoarthritis. Ten knees were collected from five cadavers within 10 hours of death and underwent a 3-Tesla MR exam including a coronal-oblique 3-dimensional fast imaging with steady state precession (3D FISP) sequence within 36 hours of death. The specimens were placed in a 4% paraformaldehyde in phosphate buffer within 58 hours of death. After preservation, a subchondral region from the tibial plateau was collected and underwent microCT imaging with a voxel size of 9 µm x 9 µm x 9 µm. A single reader analyzed the microCT images in a similar volume of interest as selected in the MR measures. A different reader analyzed the MR-based trabecular morphometry using a custom analysis tool. To analyze the MR-based trabecular morphometry, a rectangular region of interest (ROI) was positioned on the 20 central images in the proximal medial tibial subchondral bone. The primary outcome measures were MR-based and microCT-based trabecular BV/TV in the proximal medial tibia. RESULTS: The MR-based apparent BV/TV was strongly correlated with microCT-based BV/TV (r=0.83, confidence interval=0.42 to 0.96), despite the MR-based apparent BV/TV being systematically lower than measured using microCT. CONCLUSIONS: MR-based apparent BV/TV in the proximal peri-articular medial tibia has good construct validity and may represent an alternative for CT-based BV/TV.

Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study.

STUDY OBJECTIVE: To assess the feasibility, patient tolerance, pharmacokinetics, and potential effectiveness of a randomized controlled trial protocol investigating intravenous calcium chloride for the prevention of uterine atony during cesarean delivery. DESIGN: Double-blind, randomized controlled pilot trial with nested population pharmacokinetic analysis. SETTING: This study was performed at Lucile Packard Children's Hospital, from August 2018 to September 2019. PATIENTS: Forty patients with at least two risk factors for uterine atony at the time of cesarean delivery. INTERVENTIONS: One gram of intravenous calcium chloride (n = 20 patients) or a saline placebo control (n = 20 patients), in addition to standard care with oxytocin, upon umbilical cord clamping. MEASUREMENTS: The primary efficacy-related outcome was the presence of uterine atony defined as the use of a second-line uterotonic medication, surgical interventions for atony, or hemorrhage with blood loss >1000 mL. Blood loss, uterine tone numerical rating scores, serial venous blood calcium levels, hemodynamics, and potential side effects were also assessed. MAIN RESULTS: The study protocol proved feasible. The incidence of atony was 20% in parturients who received calcium compared to 50% in the placebo group (relative risk 0.38, P = 0.07, 95% CI 0.15-1.07, NNT 3.3). Calcium recipients tolerated the drug infusion well, with no adverse events and an equal incidence of potential side effects in the calcium and placebo groups. Ionized calcium concentration rose significantly in all patients who received calcium infusion, from baseline 1.18 mmol/L to peak levels 1.50-1.60 mmol/L. One-compartment population pharmacokinetics established clearance of 0.93 (95% CI 0.63-1.52) L/min and volume of distribution 76 (95% CI 49-94) L. CONCLUSIONS: In this pilot study, investigators found that intravenous calcium chloride was well-tolerated by the 20 patients assigned to receive the study drug and may be effective in prevention of uterine atony. A 1-g dose was sufficient to substantially increase calcium levels without any critically elevated lab values or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https://clinicaltrials.gov/ct2/show/NCT03867383.