Citations

Background: A recently developed mechanical impact simulator induced an anterior cruciate ligament (ACL) rupture via the application of a combination of inverse dynamics–based knee abduction moment (KAM), anterior tibial shear force (ATS), and internal tibial rotation moment with impulsive compression in a cohort of cadaveric limbs. However, there remains an opportunity to further define the interaction of internal forces and moments at the knee and their respective influence on injury events. Purpose: To identify the influence of internal knee loads on an ACL injury event using a cadaveric impact simulator. Study Design: Controlled laboratory study. Methods: Drop-landing simulations were performed and analyzed on 30 fresh-frozen cadaveric knees with a validated mechanical impact simulator. Internal forces and moments at the knee joint center were calculated using data from a 6-axis load cell recorded on the femur during testing. Kinetic data from a total of 1083 trials that included 30 ACL injury trials were used as inputs for principal component (PC) analysis to identify the most critical features of loading waveforms. Logistic regression analysis with a stepwise selection was used to select the PCs that predicted an ACL injury. Injurious waveforms were reconstructed with selected PCs in logistic regression analysis. Results: A total of 3 PCs were selected in logistic regression analysis that developed a significant model ( P < .001). The external loading of KAM was highly correlated with PC1 (ρ < –0.8; P < .001), which explained the majority (>69%) of the injurious waveforms reconstructed with the 3 selected PCs. The injurious waveforms demonstrated a larger internal knee adduction moment and lateral tibial force. After the ACL was ruptured, decreased posterior tibial force was observed in injury trials. Conclusion: These findings give us a better understanding of ACL injury mechanisms using 6-axis kinetics from an in vitro simulator. An ACL rupture was correlated with an internal knee adduction moment (external KAM) and was augmented by ATS and lateral tibial force induced by an impact, which distorted the ACL insertion orientation. Clinical Relevance: The ACL injury mechanism explained in this study may help target injury prevention programs to decrease injurious knee loading (KAM, ATS, and lateral tibial force) during landing tasks.

Abstract SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

Abstract Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder with complex biology and significant clinical heterogeneity. Many preclinical and early phase ALS clinical trials have yielded promising results that could not be replicated in larger phase 3 confirmatory trials. One reason for the lack of reproducibility may be ALS biological and clinical heterogeneity. Therefore, in this review, we explore sources of ALS heterogeneity that may reduce statistical power to evaluate efficacy in ALS trials. We also review efforts to manage clinical heterogeneity, including use of validated disease outcome measures, predictive biomarkers of disease progression, and individual clinical risk stratification. We propose that personalized prognostic models with use of predictive biomarkers may identify patients with ALS for whom a specific therapeutic strategy may be expected to be more successful. Finally, the rapid application of emerging clinical and biomarker strategies may reduce heterogeneity, increase trial efficiency, and, in turn, accelerate ALS drug development.

Study Design: Narrative review. Objective: This article seeks to provide a narrative review regarding the ability of opportunistic information available from computed tomography (CT) scans to guide decisions in spine surgery related to patient bone quality. Methods: A review of the literature (limited to human and English language) was performed via PubMed and Google Scholar using the search terms; “osteoporosis” AND “opportunistic” AND “computed tomography” AND “spine surgery.” The titles and then abstracts of all identified citations were reviewed for inclusion by 2 of the authors (MS, BAF). Relevant articles were then studied in full text. Results: A review of the literature found 25 articles that were selected for inclusion in this narrative review. These articles were broadly divided into 4 subcategories: (1) opportunistic CT (oCT) and osteoporosis detection, (2) oCT data and the quality of screw fixation, (3) utilization of Hounsfield units to assess clinical and/or radiographic outcomes following spine fusion, and (4) virtual stress testing in spine surgery. Conclusion: The literature on oCT, as well as associated virtual stress-testing techniques, demonstrate the potential to enhance spine surgery outcomes by preoperatively identifying at-risk patients in need of bone health optimization and informing best techniques for performing spinal fusion surgery on patients with diminished bone quality. While our narrative summary of the limited literature to date suggests a promising future for oCT data, significant additional research and/or radiographic workflow standardization is needed to validate these methods for clinical use.

Background: The existent literature has well explored knee ligament kinetics and strain at and after initial contact (IC) during landing tasks. However, little is known about knee ligament biomechanics in flight before IC. Purpose: To quantify and compare change in anterior cruciate ligament (ACL) and medial collateral ligament (MCL) strain before IC relative to after IC. Study Design: Descriptive laboratory study. Methods: A total of 40 cadaveric specimens were analyzed after being subjected to simulated landings in a mechanical impact simulator. External joint loads of varying magnitudes were applied to mimic relative injury risk load levels from an in vivo cohort and were coupled with an impulse force to represent initial ground contact. Implanted strain gauges continually recorded ligament strain. Kruskal-Wallis tests evaluated the significance of risk level and pre- and post-IC factors, while Wilcoxon each-pair tests evaluated differences within both factors. Results: Strain responses during simulated landing tasks for the ACL ( P ≥ .545) and MCL ( P ≥ .489) were consistent after IC regardless of the level of relative injury risk simulated in each trial. Before IC, the level of injury risk kinetics applied to a specimen differentiated strain response in the ACL ( P < .001) and MCL ( P < .001), as higher risk profiles produced greater changes in ligament strain. Mean baseline strain was 4.0% in the ACL and 1.0% in the MCL. Mean change in strain from the ACL ranged from 0.1% to 3.9% pre-IC and from 2.9% to 5.7% post-IC, while the MCL ranged from 0.0% to 3.0% pre-IC and from 0.9% to 1.3% post-IC. Conclusion: Within each ligament, post-IC strain response lacked statistical differences among simulated risk profiles, while pre-IC response was dependent on the risk profile simulated. Individually, neither pre- nor poststrain changes were enough to induce ACL failure, but when combined over the course of a full landing task, they could lead to rupture. Clinical Relevance: Prevention and rehabilitation techniques should aim to limit the presence of increased risk biomechanics in flight before landing, as impulse delivery at IC is inevitable.

Study Design. Retrospective cohort study of the Own the Bone database which is a fracture liaison service designed to improve recognition and treatment of osteoporosis. Objective. To use the Own the Bone (OTB) database to 1) examine the specific demographics of patients presenting with a low-energy clinical vertebral fracture (VFX) and 2) compare demographic and fracture-specific risk factors between patients with clinical VFX versus patients with nonvertebral low-energy fracture (NVFX). Summary of Background Data. Large database studies have described risk factors for developing VFX. It is well described that a history of previous VFX portends an increased risk of future VFX. Few studies have reported cohorts from a fracture liaison service such as the OTB initiative. Methods. 35,039 unique cases of fragility fracture occurred between 2009 and 2016 and were included in analysis. VFX accounted for 3395 (9.9%) of the presenting fractures at OTB enrollment. The demographics, lifestyle factors, medication use, and fracture-specific data for patients in the OTB registry with vertebral fractures were summarized and then statistically compared to those with nonvertebral fragility fractures. Results. The majority of VFX patients were Caucasian, postmenopausal women (74.4%). There was an increased likelihood of presenting with a vertebral fracture in patients who sustained a previous VFX after the age of 50, while patients who sustained a prior nonvertebral fracture (NVFX) were more likely to present with a subsequent NVFX. After controlling for patients with a history of fracture after the age of 50, VFX patients (vs. NVFX) were more likely to be age 70–79, class 1 obesity, with a history of taking anti-osteoporotic prescription medications. Conclusions. Multiple factors were associated with a significantly increased risk of VFX compared with NVFX. Understanding the risk factors unique to fragility VFX is a critical component for targeting “at-risk” patients and preventing future osteoporosis-related fractures and their consequences. Level of Evidence: 4

AbstractObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy‐two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint] = 0.14) or physician trust more in parents with low health literacy (Pint = 0.34). The decision aid decreased decisional conflict more in non‐white parents (decisional conflict scale, −8.14, 95% CI: −12.33 to −3.95; Pint = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35‐14.83; Pint = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non‐white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.