Inhibition of bone repair in a rat model for chronic and excessive alcohol consumption.

Alcohol abuse is associated with increases in both the incidence of fractures and complications in fracture healing. The purpose of this study was to determine the dose-dependent effects of ethanol on bone repair in a rat model. Three-month-old male Wistar rats were continuously fed liquid diets containing ethanol as either 36% or 26% of total calories or control diets for 6 weeks. Then, a bone repair model was created in all rats. Bone healing and liver metabolism were evaluated 7 weeks after bone injury. For each dose, there were three ethanol-feeding groups receiving (1) ethanol for 13 weeks, (2) control diet for 13 weeks (pair-fed), and (3) ethanol before bone injury and control diet (pair-fed) after injury. Another group was fed ethanol (36%) before injury and given control diet ad libitum after injury. There were also two nutritional controls consuming control diet and standard rat chow ad libitum for 13 weeks. Abnormal liver metabolism was evident at the higher ethanol dose - increases in cytochrome P4502E1 specific activity (5-fold; P < .01), triglyceride content (4-fold; P < .02), and liver weight (25%; P = .05) - compared with pair-fed controls. The higher dose of ethanol resulted in deficient bone repair when compared with rats receiving ethanol-free control diet by pair-feeding: 26% less (P = .02) rigidity of the repaired bone, 41% less (P = .02) intrinsic stiffness, 24% less intrinsic strength (P = .05), and 14% less (P = .001) ash density of the repair tissue. The reduced food consumption of ethanol-fed rats compared with that in the nutritional controls did not contribute to this deficiency. Furthermore, removal of ethanol (as 36% of calories) from the diet after bone injury completely restored normal bone healing and nearly normalized the liver metabolism. The lower ethanol dose (26% of calories) had a minimal effect on liver metabolism and bone repair. We conclude that ethanol (as 36% of calories) in the rat diet, especially during the postinjury period, was solely responsible for the observed inhibition of bone repair.     

Consensus statement on prevention and management of adverse effects following rejuvenation procedures with hyaluronic acid‐based fillers

Facial fillers play an important role in the correction of facial changes associated with ageing. They offer quick treatments in the outpatient setting with minimal subsequent downtime that provide predictable, natural‐looking, long‐lasting results. Adverse reactions after hyaluronic acid injections tend to be mild or moderate and rather temporary. However, as with all injected or implanted biomaterials, severe adverse events can occur and patients must be fully informed of potential risks prior to undergoing treatment. A panel of experts from Germany (D), Austria (A) and Switzerland (CH) developed recommendations, and this study provides the ‘DACH Consensus Recommendations’ from this group specifically on the use of hyaluronic acid fillers. The aim is to help clinicians recognize potential risks and to provide guidance on how best to treat adverse events if they arise. Contraindications to hyaluronic acid fillers are also detailed, and ways to prevent adverse events occurring are discussed. Hyaluronic acid‐based products are claimed to be very close to an ideal tissue augmentation agent; nevertheless, profound medical, anatomical and product knowledge are of paramount importance to minimize the occurrence of adverse reactions.     

The Utility of Shear-Wave Elastography in the Evaluation of Myositis

Changes in muscle elasticity are expected in patients with untreated myositis. The purpose of this study was to define the accuracy of shear-wave elastography (SWE) in diagnosing myositis. This case control study included 21 patients (mean age, 49.4 y; 12 women) with myositis who underwent SWE, magnetic resonance imaging (MRI) and biopsy of the involved muscle group. SWE was performed accordingly in a control group (n = 24; mean age, 51.2 y; 8 women). Blood tests consisted of creatine kinase (CK) and aldolase. Two operators performed SWE in longitudinal and transverse planes of muscular fibers, quantifying the mean shear-wave velocity (SWV) and the pattern of stiffness. On MRI, short-TI inversion recovery (STIR) signal hyperintensity and T1 contrast enhancement of muscle was considered diagnostic for myositis. The patient group suffered from different types of myositis (nine patients with polymyositis, eight with dermatomyositis and four with other types of myositis). Blood tests showed significantly increased CK and aldolase values in patients with myositis (p < 0.001 and p < 0.0001). MRI showed a sensitivity of 0.95. In the patient group, the mean SWVs of longitudinal and transverse measurements were 2.8 ± 1.4 m/s and 3.1 ± 1.2 m/s, respectively. In the control group, SWVs were 2.3 ± 0.5 m/s and 2.4 ± 0.5 m/s, respectively. The difference between transverse measurements was significant (p = 0.02). Increased heterogeneity as a marker for myositis in transverse SWE showed a sensitivity of 0.8, specificity of 0.79, positive predictive value (PPV) of 0.76 and negative predictive value (NPV) of 0.82. Inter-observer difference was very low (κ = 0.92). Increased heterogeneity in both planes compared with histologic results showed a sensitivity of 0.56, specificity of 0.93, PPV of 0.91 and NPV of 0.62. Spearman correlation between CK <1000 U/L and SWE was 0.54. In conclusion, transverse orientation SWE may serve as an imaging biomarker for the diagnosis of myositis through the display of a heterogeneous pattern and increased absolute SWV values of inflamed muscles.     

An Exponential Decay Model for Mediation

Mediation analysis is often used to investigate mechanisms of change in prevention research. Results finding mediation are strengthened when longitudinal data are used because of the need for temporal precedence. Current longitudinal mediation models have focused mainly on linear change, but many variables in prevention change nonlinearly across time. The most common solution to nonlinearity is to add a quadratic term to the linear model, but this can lead to the use of the quadratic function to explain all nonlinearity, regardless of theory and the characteristics of the variables in the model. The current study describes the problems that arise when quadratic functions are used to describe all nonlinearity and how the use of nonlinear functions, such as exponential decay, address many of these problems. In addition, nonlinear models provide several advantages over polynomial models including usefulness of parameters, parsimony, and generalizability. The effects of using nonlinear functions for mediation analysis are then discussed and a nonlinear growth curve model for mediation is presented. An empirical example using data from a randomized intervention study is then provided to illustrate the estimation and interpretation of the model. Implications, limitations, and future directions are also discussed.