Noninvasive tests for arterial structure, function, and compliance: do they identify risk or diagnose disease?

BACKGROUND: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk for CAD developing. METHODS: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. RESULTS: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P =.01); smoking history (P =.002); hypercholesterolemia (P =.002); and hypertension (P =.004) (model R = 0.82; P =.0001). The independent predictors of CAD were: IMT (P =.001); BAR (P =.04); sex (P =.005); and hypertension (P =.005) (model R = 0.80; P =.0001). CONCLUSION: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.     

Screw angulation affects bone-screw stresses and bone graft load sharing in anterior cervical corpectomy fusion with a rigid screw-plate construct: a finite element model study

Background contextAnterior corpectomy and reconstruction with bone graft and a rigid screw-plate construct is an established procedure for treatment of cervical neural compression. Despite its reliability in relieving symptoms, there is a high rate of construct failure, especially in multilevel cases.PurposeThere has been no study evaluating the biomechanical effects of screw angulation on construct stability; this study investigates the C4–C7 construct stability and load-sharing properties among varying screw angulations in a rigid plate-screw construct.Study designA finite element model of a two-level cervical corpectomy with static anterior cervical plate.MethodsA three-dimensional finite element (FE) model of an intact C3–T1 segment was developed and validated. From this intact model, a fusion model (two-level [C5, C6] anterior corpectomy) was developed and validated. After corpectomy, allograft interbody fusion with a rigid anterior screw-plate construct was created from C4 to C7. Five additional FE models were developed from the fusion model corresponding to five different combinations of screw angulations within the vertebral bodies (C4, C7): (0°, 0°), (5°, 5°), (10°, 10°), (15°, 15°), and (15°, 0°). The fifth fusion model was termed as a hybrid fusion model.ResultsThe stability of a two-level corpectomy reconstruction is not dependent on the position of the screws. Despite the locked screw-plate interface, some degree of load sharing is transmitted to the graft. The load seen by the graft and the shear stress at the bone-screw junction is dependent on the angle of the screws with respect to the end plate. Higher stresses are seen at more divergent angles, particularly at the lower level of the construct.ConclusionThis study suggests that screw divergence from the end plates not only increases load transmission to the graft but also predisposes the screws to higher shear forces after corpectomy reconstruction. In particular, the inferior screw demonstrated larger stress than the upper-level screws. In the proposed hybrid fusion model, lower stresses on the bone graft, end plates, and bone-screw interface were recorded, inferring lower construct failure (end-plate fractures and screw pullout) potential at the inferior construct end.     

Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro

ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation.     

Understanding the minimum clinically important difference: a review of concepts and methods.

BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is currently evaluated through the assessment of patient-reported outcomes (PROs). The minimum clinically important difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment. PURPOSE: Our goal is to review the various definitions of MCID and the methods available to determine MCID. STUDY DESIGN: The primary means of determining the MCID for a specific treatment are divided into anchor-based and distribution-based methods. Each method is further subdivided and examined in detail. METHODS: The overall limitations of the MCID concept are first identified. The basic assumptions, statistical biases, and shortcomings of each method are examined in detail. RESULTS: Each method of determining the MCID has specific shortcomings. Three general limitations in the accurate determination of an MCID have been identified: the multiplicity of MCID determinations, the loss of the patient's perspective, and the relationship between pretreatment baseline and posttreatment change scores. CONCLUSIONS: An ideal means of determining the MCID for a given intervention is yet to be determined. It is possible to develop a useful method provided that the assumptions and methodology are initially declared. Our efforts toward the establishment of a MCID will rely on the establishment of specific external criteria based on the symptoms of the patient and treatment intervention being evaluated.     

Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice

Insulin-like growth factor-1 (Igf-1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia-inducible factor 1-alpha (Hif-1alpha) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf-1 are responsible for the reduction in Hif-1alpha protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1alpha protein synthesis and activity during wound repair. In addition, Igf-1 stimulated phosphytidylinositol 3-kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF-1 protein was associated with an increase in Hif-1alpha protein synthesis and function in vivo.