The goal of this study was to assess the immunogenicity and antigenicity of StrataGraft skin tissue in a randomized phase I/II clinical trial for the temporary management of full-thickness skin loss.
Summary Background Data
StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully-stratified, biologically active epidermis derived from NIKS cells, a pathogen-free, long-lived, consistent, human keratinocyte progenitor.
Traumatic skin wounds often require temporary allograft coverage to stabilize the wound bed until autografting is possible. StrataGraft and cadaveric allograft were placed side-by-side on 15 patients with full-thickness skin defects for one week prior to autografting. Allografts were removed from the wound bed and examined for allogeneic immune responses. Immunohistochemistry and indirect immunofluorescence were used to assess tissue structure and cellular composition of allografts. In vitro lymphocyte proliferation assays, chromium-release assays, and development of antibodies were used to examine allogeneic responses.
One week after patient exposure to allografts, there were no differences in the numbers of T or B lymphocytes or Langerhans cells present in StrataGraft skin substitute compared to cadaver allograft, the standard of care. Importantly, exposure to StrataGraft skin substitute did not induce the proliferation of patient peripheral blood mononuclear cells to NIKS keratinocytes or enhance cell-mediated lysis of NIKS keratinocytes in vitro. Similarly, no evidence of antibody generation targeted to the NIKS keratinocytes was seen.
These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds. Notably, exposure to StrataGraft did not increase patient sensitivity toward or elicit immune responses against the NIKS keratinocytes. We envision this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.
BACKGROUND: Although measurement of whole-blood creatinine at the point of care offers rapid assessment of renal function, agreement of point-of-care (POC) results with central laboratory methods continues to be a concern. We assessed the influence of several potential interferents on POC whole-blood creatinine measurements.
BackgroundThe Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method.MethodsMethod comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk.ResultsWe obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit.ConclusionThe Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.
Background: In a planned International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) worldwide study on reference intervals (RIs), a common panel of serum samples is to be measured by laboratories from different countries, and test results are to be compared through conversion using linear regression analysis. This report presents a validation study that was conducted in collaboration with four laboratories. Methods: A panel composed of 80 sera was prepared from healthy individuals, and 45 commonly tested analytes (general chemistry, tumor markers, and hormones) were measured on two occasions 1 week apart in each laboratory. Reduced major-axis linear regression was used to convert reference limits ( LL and UL ). Precision was expressed as a ratio of the standard error of converted LL or UL to the standard deviation (SD) comprising RI (approx. 1/4 of the RI width corresponding to between-individual SD). The allowable and optimal levels of error for the SD ratio (SDR) were set as ≤ 0.250 and ≤ 0.125, respectively, in analogy to the common method of setting limits for analytical bias based on between-individual SD.
α(1)-Antitrypsin (AAT) deficiency leads to deterioration of the lungs that can be prevented with diagnosis and treatment. Isoelectric focusing (IEF) electrophoresis is the current biochemical gold standard for detecting AAT deficiency variants but involves complex interpretation. Variant AAT samples were collected over a 2-year period. Stability of AAT for phenotype determination was assessed in whole blood, dried blood spots, and dried serum spots. A compendium displaying 13 common and 5 rare AAT phenotypes was created, and a detailed methodology describing how to recognize AAT banding patterns and interpret a rare phenotype accompanied these visual data. AAT was stable for IEF phenotype analysis for at least 1 week in whole blood and for 24 hours on dried serum spots. In conclusion, a reference compendium of known AAT phenotypes was established that can serve as a resource for interpreting AAT phenotypes.
scite is a Brooklyn-based startup that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.