Novel Neonatal Umbilical Catheter Protection and Stabilization Device in In vitro Model of Catheterized Human Umbilical Cords: Effect of Material and Venting on Bacterial Colonization.

OBJECTIVE: Umbilical central lines deliver life-saving medications and nutrition for neonates; however, complications associated with umbilical catheters (UCs) occur more frequently than in adults with central lines (i.e., line migration, systemic infection). We have developed a device for neonatal UC protection and stabilization to reduce catheter exposure to bacteria compared with the standard of care: "goal post" tape configuration. This study analyzes the effect of device venting and material on bacterial load of human umbilical cords in vitro. STUDY DESIGN: Catheters were inserted into human umbilical cord segments in vitro, secured with plastic or silicone vented prototype versus tape, and levels of bacterial colonization were compared between groups after 7 days of incubation. RESULTS: Nonvented plastic prototype showed increased bacterial load compared with goal post (p = 0.04). Colonization was comparable between the goal post and all vented plastic prototypes (p ≥ 0.30) and when compared with the vented silicone device (p = 1). CONCLUSION: A novel silicone device does not increase external bacterial colonization compared with the current standard of care for line securement, and may provide a safe, convenient alternative to standard adhesive tape for UC stabilization. Future studies are anticipated to establish safety in vivo, alongside benefits such as migration and infection reduction.

Cartilage Subsurface Changes to Magnetic Resonance Imaging UTE-T2* 2 Years After Anterior Cruciate Ligament Reconstruction Correlate With Walking Mechanics Associated With Knee Osteoarthritis.

BACKGROUND: Anterior cruciate ligament (ACL) injury increases risk for posttraumatic knee osteoarthritis (OA). Quantitative ultrashort echo time enhanced T2* (UTE-T2*) mapping shows promise for early detection of potentially reversible subsurface cartilage abnormalities after ACL reconstruction (ACLR) but needs further validation against established clinical metrics of OA risk such as knee adduction moment (KAM) and mechanical alignment. HYPOTHESIS: Elevated UTE-T2* values in medial knee cartilage 2 years after ACLR correlate with varus alignment and higher KAM during walking. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Twenty patients (mean age, 33.1 ± 10.5 years; 11 female) 2 years after ACLR underwent 3.0-T knee magnetic resonance imaging (MRI), radiography, and gait analysis, after which mechanical alignment was measured, KAM during walking was calculated, and UTE-T2* maps were generated. The mechanical axis and the first and second peaks of KAM (KAM1 and KAM2, respectively) were tested using linear regressions for correlations with deep UTE-T2* values in the central and posterior medial femoral condyle (cMFC and pMFC, respectively) and central medial tibial plateau (cMTP). UTE-T2* values from ACL-reconstructed patients were additionally compared with those of 14 uninjured participants (mean age, 30.9 ± 8.9 years; 6 female) using Mann-Whitney U and standard t tests. RESULTS: Central weightbearing medial compartment cartilage of ACL-reconstructed knees was intact on morphological MRI. Mean UTE-T2* values were elevated in both the cMFC and pMFC of ACL-reconstructed knees compared with those of uninjured knees ( P = .003 and P = .012, respectively). In ACL-reconstructed knees, UTE-T2* values of cMFC cartilage positively correlated with increasing varus alignment ( R = 0.568). Higher UTE-T2* values in cMFC and cMTP cartilage of ACL-reconstructed knees also correlated with greater KAM1 ( R = 0.452 and R = 0.463, respectively) and KAM2 ( R = 0.465 and R = 0.764, respectively) and with KAM2 in pMFC cartilage ( R = 0.602). CONCLUSION: Elevated deep UTE-T2* values of medial knee cartilage 2 years after ACLR correlate with 2 clinical markers of increased risk of medial knee OA. These results support the clinical utility of MRI UTE-T2* for early diagnosis of subsurface cartilage abnormalities. Longitudinal follow-up of larger cohorts is needed to determine the predictive and staging potential of UTE-T2* for posttraumatic OA.

Baseline ambulatory knee kinematics are associated with changes in cartilage thickness in osteoarthritic patients over 5 years.

Although kinematic alterations during walking have been reported with knee osteoarthritis (OA), there is a paucity of longitudinal data, therefore limiting our understanding of the role of kinematics in OA development. This study tested the hypothesis that less knee extension angle and less posterior displacement of the femur relative to the tibia during the heel-strike portion of the gait cycle are associated with greater loss of medial cartilage thickness during a follow-up period of five years. This study also tested for associations between flexion-extension angle and anterior-posterior displacement during other periods of the gait cycle and 5-year cartilage thinning. 16 subjects with moderate medial knee OA were tested with gait analysis and MRI at baseline and had a follow-up MRI after 5 years. Linear regressions were used to assess the relationship between changes in cartilage thickness and baseline kinematics using Pearson correlation coefficients. Multivariate regressions were also performed to adjust for gender, baseline age, BMI, walking speed, Kellgren/Lawrence grade, and baseline knee pain score. As hypothesized, baseline knee flexion angle and femoral displacement during heel-strike and other gait cycle periods were significantly associated with medial femoral and tibial cartilage thinning at the 5 year follow-up; these associations were strengthened after adjustment for covariates. This study provided new insight into the pathogenesis of knee OA where baseline knee kinematics were associated with longitudinal disease progression. These results could serve as a basis for developing newer gait modification interventions to reduce the risk for developing knee OA.

General scheme to reduce the knee adduction moment by modifying a combination of gait variables.

Reducing the knee adduction moment (KAM) is a promising treatment for medial compartment knee osteoarthritis (OA). Although several gait modifications to lower the KAM have been identified, the potential to combine modifications and individual dose-responses remain unknown. This study hypothesized that: (i) there is a general scheme consisting of modifications in trunk sway, step width, walking speed, and foot progression angle that reduces the KAM; (ii) gait modifications can be combined; and (iii) dose-responses differ among individuals. Walking trials with simultaneous modifications in step width, walking speed, progression angle, and trunk sway were analyzed for 10 healthy subjects. Wider step width, slower speed, toeing-in, and increased trunk sway resulted in reduced first KAM peak, whereas wider step width, faster speed, and increased trunk sway reduced the KAM angular impulse. Individual regressions accurately modeled the amplitude of the KAM variables relative to the amplitude of the gait modification variables, while the dose-responses varied strongly among participants. In conclusion, increasing trunk sway, increasing step width, and toeing-in are three gait modifications that could be combined to reduce KAM variables related to knee OA. Results also indicated that some gait modifications reducing the KAM induced changes in the knee flexion moment possibly indicative of an increase in knee loading. Taken together with the different dose-responses among subjects, this study suggested that gait retraining programs should consider this general scheme of modifications with individualization of the modification amplitudes. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1547-1556, 2016.

Mechanical feasibility of immediate mobilization of the brachioradialis muscle after tendon transfer.

PURPOSE: Tendon transfer is often used to restore key pinch after cervical spinal cord injury. Current postoperative recommendations include elbow immobilization in a flexed position to protect the brachioradialis-flexor pollicis longus (BR-FPL) repair. The purpose of this study was to measure the BR-FPL tendon tension across a range of wrist and elbow joint angles to determine whether joint motion could cause repair rupture. METHODS: We performed BR-to-FPL tendon transfers on fresh-frozen cadaveric arms (n = 8) and instrumented the BR-FPL tendon with a buckle transducer. Arms were ranged at 4 wrist angles from 45 degrees of flexion to 45 degrees of extension and 8 elbow angles from 90 degrees of flexion to full extension, measuring tension across the BR-FPL repair at each angle. Subsequently, the BR-FPL tendon constructs were removed and elongated to failure. RESULTS: Over a wide wrist and elbow range of motion, BR-FPL tendon tension was under 20 N. Two-way analysis of variance with repeated measures revealed a significant effect of wrist joint angle (p<.001) and elbow joint angle (p<.001) with significant interaction between elbow and joint angles (p<.001). Because the failure load of the repair site was 203 +/- 19 N, over 10 times the loads that would be expected to occur at the repair site, our results demonstrate that the repair has a safety factor of at least 10. CONCLUSIONS: Our tendon force measurements support the assertion that the elbow joint need not be immobilized when the BR is used as a donor muscle in tendon transfer to the FPL. This is based on the fact that maximum passive tendon tension was only about 20 N in our cadaveric model and the failure strength of this specific repair was over 200 N. We suggest that it is possible to consider performing multiple tendon transfers in a single stage, avoiding immobilization, which may adversely affect functional recovery. These results must be qualified by the fact that issues unique to living tissues such as postoperative edema and tendon gliding cannot be accounted for by this cadaveric model.

Effects of FoxO4 overexpression on cholesterol biosynthesis, triacylglycerol accumulation, and glucose uptake.

The Forkhead transcription factors FoxO1, FoxO3a, and FoxO4 play a prominent role in regulating cell survival and cell cycle. Whereas FOXO1 was shown to mediate insulin sensitivity and adipocyte differentiation, the role of the transcription factor FoxO4 in metabolism remains ill defined. To uncover the effects of FoxO4, we generated a cellular model of stable FoxO4 overexpression and subjected it to microarray-based gene expression profiling. While pathway analysis revealed a disruption of cholesterol biosynthesis gene expression, biochemical studies revealed an inhibition of cholesterol biosynthesis, which was coupled with decreased mRNA levels of lanosterol 14alpha demethylase (CYP51). FoxO4-mediated repression of CYP51 led to the accumulation of 24,25 dihydrolano-sterol (DHL), which independently and unlike lanosterol inhibited cholesterol biosynthesis. Furthermore, FoxO4-overexpressing cells accumulated lipid droplets and triacylglycerols and had an increase in basal glucose uptake. Recapitulation of these effects was obtained following treatment with CYP51 inhibitors, which also induce DHL buildup. Moreover, DHL but not lanosterol strongly stimulated liver X receptor alpha (LXRalpha) activity, suggesting that DHL and LXRalpha mediate the downstream effects initiated by FoxO4. Together, these studies suggest that FoxO4 acts on CYP51 to regulate the late steps of cholesterol biosynthesis.

Overexpression of the transcription factor Foxo4 is associated with rapid glucose clearance.

Leptin treatment ameliorates lipoatrophic diabetes in animal models and humans. Transgenic mice overexpressing leptin (LepTg) are lipoatrophic but not diabetic and thus represent a model for elucidating mechanisms of leptin-mediated glucose homeostasis. In this communication, we show that LepTg mice overexpress the forkhead transcription factor foxo4 in their remnant adipose tissue. To further characterize the role of foxo4 in adipose tissue, we generated transgenic mice overexpressing a constitutive active form of foxo4 (A3foxo4) under the control of the aP2 promoter/enhancer. aP2-A3foxo4 mice are not lipoatrophic but are able to clear glucose rapidly similar to LepTg mice. In addition, both LepTg and A3foxo4 mice show in their adipocytes increased AMP-activated protein kinase (AMPK) phosphorylation, suggesting a link between AMPK, glucose clearance, foxo4 and the leptin axis. These studies shed new light on mechanisms by which leptin treatment improves glucose disposal.