Development of outcome measures for autoimmune dermatoses

Validated outcome measures are essential in monitoring disease severity. Specifically in dermatology, which relies heavily on the clinical evaluation of the patient and not on laboratory values and radiographic tests, outcome measures help standardize patient care. Validated cutaneous scoring systems, much like standardized laboratory values, facilitate disease management and follow therapeutic response. Several cutaneous autoimmune dermatoses, specifically cutaneous lupus erythematosus (CLE), dermatomyositis (DM), and pemphigus vulgaris (PV), lack such outcome measures. As a result, evaluation of disease severity and patients’ response to therapy over time is less reliable. Ultimately, patient care is compromised. These diseases, which are often chronic and relapsing and remitting, are also often refractory to treatment. Without outcome measures, new therapies cannot be systematically assessed in these diseases. Clinical trials that are completed without standardized outcome measures produce less reliable results. Therefore, the development of validated outcome measures in these autoimmune dermatoses is critical. However, the process of developing these tools is as important, if not more so, than their availability. This review examines the steps that should be considered when developing outcome measures, while further examining their importance in clinical practice and trials. Finally, this review more closely looks at CLE, DM, and PV and addresses the recent and ongoing progress that has been made in the development of their outcome measures

The effect of starting point placement technique on thoracic transverse process strength: an ex vivo biomechanical study

<p>Abstract</p> <p>Background</p> <p>The use of thoracic pedicle screws in spinal deformity, trauma, and tumor reconstruction is becoming more common. Unsuccessful screw placement may require salvage techniques utilizing transverse process hooks. The effect of different starting point placement techniques on the strength of the transverse process has not previously been reported. The purpose of this paper is to determine the biomechanical properties of the thoracic transverse process following various pedicle screw starting point placement techniques.</p> <p>Methods</p> <p>Forty-seven fresh-frozen human cadaveric thoracic vertebrae from T2 to T9 were disarticulated and matched by bone mineral density (BMD) and transverse process (TP) cross-sectional area. Specimens were randomized to one of four groups: A, control, and three others based on thoracic pedicle screw placement technique; B, straightforward; C, funnel; and D, in-out-in. Initial cortical bone removal for pedicle screw placement was made using a burr at the location on the transverse process or transverse process-laminar junction as published in the original description of each technique. The transverse process was tested measuring load-to-failure simulating a hook in compression mode. Analysis of covariance and Pearson correlation coefficients were used to examine the data.</p> <p>Results</p> <p>Technique was a significant predictor of load-to-failure (<it>P </it>= 0.0007). The least squares mean (LS mean) load-to-failure of group A (control) was 377 N, group B (straightforward) 355 N, group C (funnel) 229 N, and group D (in-out-in) 301 N. Significant differences were noted between groups A and C, A and D, B and C, and C and D. BMD (0.925 g/cm²[range, 0.624-1.301 g/cm²]) was also a significant predictor of load-to-failure, for all specimens grouped together (<it>P </it>< 0.0001) and for each technique (<it>P <</it>0.05). Level and side tested were not found to significantly correlate with load-to-failure.</p> <p>Conclusions</p> <p>The residual coronal plane compressive strength of the thoracic transverse process is dependent upon the screw starting point placement technique. The funnel technique significantly weakens transverse processes as compared to the straightforward technique, which does not significantly weaken the transverse process. It is also dependent upon bone mineral density, and low failure loads even in some control specimens suggest limited usefulness of the transverse process for axial compression loading in the osteoporotic thoracic spine.</p

Scabies Mite Peritrophins Are Potential Targets of Human Host Innate Immunity

The gut of most invertebrates is lined by a protective layer of chitin and glycoproteins, often designated as a peritrophic matrix. Previous research suggests that it forms a barrier that may protect the midgut epithelium from abrasive food particles and pathogens. Parasitic invertebrates ingesting vertebrate plasma have evolved additional strategies to protect themselves from hazardous host molecules consumed during feeding. An important part of the immediate defense in vertebrate plasma is complement-mediated killing. The Complement system is a complex network of more than 35 proteins present in human plasma that results in killing of foreign cells including the gut epithelial cells of a feeding parasite. Recently we found that scabies mites, who feed on skin containing plasma, produce several proteins that inhibit human complement within the mite gut. The mites excrete these molecules into the upper epidermis where they presumably also inhibit complement activity. Mite gut antigens that initially trigger the complement cascade have not been identified previously. Obvious possible targets of complement attack within the mite gut could be peritrophins. Our study describes the first peritrophin identified in scabies mites and indicates a possible role in complement activation