Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

The difficulty of diagnosing NCSE in clinical practice; external validation of the Salzburg criteria

To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount. We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE. Of the 191 EEG recordings, 12 (12%) was classified as an NCSE according to the reference standard. In the validation cohort, sensitivity was 67% and specificity was 89%. The positive predictive value was 47% and the negative predictive value was 95%. Ten patients in the control group (n = 93) were false positive, resulting in a specificity of 89.2%. The interrater agreement between the reference standards and between the scorers of the Salzburg criteria was moderate; disagreement occurred mainly in patients with an epileptic encephalopathy. The Salzburg criteria showed a lower diagnostic accuracy in our external validation study than in the original design, suggesting that they cannot replace the current practice of careful weighing of both clinical and EEG information on an individual basis.     

Prosthetic use in elderly patients with dysvascular above-knee and through-knee amputations

Fifty-five patients with vascular insufficiency resulting in above-knee (AK) and through-knee (TK) amputations were studied to determine factors related to prosthetic candidacy and functional outcome. Chart review showed that the only difference between patients who were fitted with prostheses and those who were not fitted with prostheses was their respective number of medical complications. Twenty-three of 31 patients with prostheses were evaluated 7 to 35 months after receiving the prostheses. Ten (44%) of these patients wore their prostheses all day every day and used wheelchairs minimally or not at all. Over half of the patients evaluated used their wheelchairs most of the time. Two (9%) of the 23 patients had stopped wearing their prostheses. Patients who demonstrated increased walking distances and velocities at follow-up used their prostheses more and their wheelchairs less than did the other patients. Neither gait factors nor hip range of motion at discharge was predictive of continued prosthetic use. Functional outcome and prosthetic use were limited in this group of elderly patients with dysvascular AK and TK amputations. The results of this study may serve as a basis for clinical determination of prosthetic candidacy and functional goals.     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

Correspondence between theoretical models and dual energy X-ray absorptiometry measurements of femoral cross-sectional growth during adolescence

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9–26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.