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.

Objective: Faulty neuromuscular and biomechanical deficits of the knee are nearly ubiquitous in athletes after anterior cruciate ligament (ACL) reconstruction (ACLR). Knee biomechanical deficits are directly associated with an increased risk of second ACL injury, which typically occurs during a sports-related movement on a single limb. To date, the biomechanical effects of a neuromuscular training (NMT) program on knee biomechanics during a single-leg landing task have not been investigated. Design: Prospective Cohort Study. Setting: Controlled laboratory setting. Participants: Eighteen ACLR and 10 control athletes. Interventions: Neuromuscular training. Main Outcome Measures: Knee kinematics and kinetics. Results: There were no significant interactions of session and limb (P > 0.05) for the athletes with ACLR after training. However, there were several significant main effects of session (P < 0.05) for knee kinematics and kinetics during the single-leg landing task. After training, the athletes with ACLR landed with greater knee flexion angles, decreased knee abduction angles, increased knee flexion range of motion, and decreased knee excursion. Also, the ACLR athletes landed with lower knee flexion moments, greater knee adduction moments, and lower peak vertical ground reaction force. Post-training comparison of the ACLR and control cohorts found no significant interactions of group and limb (P > 0.05) and only a significant main effect of group (P < 0.05) for frontal plane knee angle at initial contact. The athletes with ACLR landed with greater knee adduction angles than the control group. Conclusions: Deficits in knee biomechanics that are associated with an increased risk of ACL injury are attenuated after completion of this NMT program.

Objective IgG4‐related disease (IgG4‐ RD ) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4‐ RD . Methods An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology ( ACR ) and the European League Against Rheumatism ( EULAR ). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included. Results A 3‐step classification process was developed. First, it must be demonstrated that a potential IgG4‐ RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4‐ RD . Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4‐ RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI ] 97.2–99.8%) and a sensitivity of 85.5% (95% CI 81.9–88.5%). In the second, the specificity was 97.8% (95% CI 93.7–99.2%) and the sensitivity was 82.0% (95% CI 77.0–86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. Conclusion ACR / EULAR classification criteria for IgG4‐ RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.

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.

Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.

AbstractIntroductionOur research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS).MethodsA prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy‐seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro‐Quality of Life (QoL), Schwab‐England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment.ResultsThe PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test‐retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS‐R were significantly higher.DiscussionThe PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period.

Objective This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC). Design All human tissue samples were from the muscularis externa of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array. Upregulated miRNAs were examined by quantitative reverse transcription qPCR (RT-qPCR) in a validation cohort of seven patients with STC and age/sex-matched controls. The effect of a highly differentially expressed miRNA on a custom human smooth muscle cell line was examined in vitro by RT-qPCR, electrophysiology, traction force microscopy, and ex vivo by lentiviral transduction in rat muscularis externa organotypic cultures. Results The expression of 13 miRNAs was increased in STC samples. Of those miRNAs, four were predicted to target SCN5A , the gene that encodes the Na + channel Na V 1.5. The expression of SCN5A mRNA was decreased in STC samples. Let-7f significantly decreased Na + current density in vitro in human smooth muscle cells. In rat muscularis externa organotypic cultures, overexpression of let-7f resulted in reduced frequency and amplitude of contraction. Conclusions A small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na + channel Na V 1.5. Within this set, a novel Na V 1.5 regulator, let-7f, resulted in decreased Na V 1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest Na V 1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose‐derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC‐seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin‐eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose‐derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.