[Retrospective computation of the ISS in multiple trauma patients: Potential pitfalls and limitations of findings in full body CT scans]. / Retrospektive Berechnung des ISS bei polytraumatisierten Patienten: Fehlerquellen und Anforderungen an den radiologischen Befund der Ganzkörper-CT.

INTRODUCTION: The Injury Severity Score (ISS) is a well-established anatomical scoring system for polytraumatized patients. However, any inaccuracy in the Abbreviated Injury Score (AIS) directly increases the ISS impreciseness. Using the full body computed tomography (CT) scan report, ISS computation can be associated with certain pitfalls. This study evaluates interpretation variations depending on radiological reports and indicates requirements to reliably determine the ISS. MATERIALS AND METHODS: The ISS of 81 polytraumatized patients was calculated based on the full body CT scan report. If an injury could not be attributed to a precise AIS cipher, the minimal and maximal ISS was computed. Real ISS included all conducted investigations, intraoperative findings, and final medical reports. The differences in ISS min, ISS max, and ISS real were evaluated using the Kruskal-Wallis test (p<0.05) and plotted in a linear regression analysis. RESULTS: Mean ISS min was 24.0 (± 0.7 SEM) points, mean ISS real 38.6 (±1.3 SEM) and mean ISS max was 48.3 (±1.4 SEM) points. All means were significantly different compared to one another (p<0.001). The difference between possible and real ISS showed a distinctive variation. Mean deviation was 9.7 (±0.9 SEM) points downward and 14.5 (±1.1 SEM) points upward. The difference between deviation to ISS min and ISS max was highly significant (p<0.001). CONCLUSION: Objectification of injury severity in polytraumatized patients using the ISS is an internationally well-established method in clinical and scientific settings. The full body CT scan report must meet distinct criteria and has to be written in acquaintance to the AIS scale if intended to be used for correct ISS computation.

[Relevance of Vascular Trauma in Trauma Care - Impact on Clinical Course and Mortality]. / Bedeutung des Gefäßtraumas für die Schwerverletztenversorgung ­ Einfluss auf Verlauf und Mortalität.

There is a lack of evidence as to the relevance of vascular trauma (VT) in patients with severe injuries. Therefore, we reviewed registry data in the present study in order to systematically objectify the effect of VT in these patients. This study aimed to provide an adequate picture of the relevance of vascular trauma and to identify adverse prognostic factors. In a retrospective analysis of records from the TraumaRegister DGU® (TR-DGU) in two subgroups with moderate and severe VT, we examined the records for differences in terms of morbidity, mortality, follow-up and prognostic parameters compared to patients without VT with the same ISS. From a total of 42,326 patients, 2,961 (7 %) had a VT, and in 2,437 cases a severe VT (AIS ≥ 3) was diagnosed (5.8 %). In addition to a higher incidence of shock and a 2 to 3-fold increase in fluid replacement and erythrocyte transfusion, patients with severe VT had a 60 % higher rate of multiple organ failure, and in-hospital mortality was twice as high (33.8 %). The massively increased early mortality (8.0 vs. 25.2 %) clearly illustrates how severely injured patients are placed at risk by the presence of a relevant VT with a comparable ISS. In our opinion, due to an unexpected poor prognosis in the TR-DGU data for vascular injuries, increased attention is required in the care of severely injured patients. Based on our comprehensive analysis of negative prognostic factors, a further adjustment to the standards of vascular medicine could be advisable. The influence of the level of care provided by the admitting hospital and the relevance of a further hospital transfer to prognosis and clinical outcome is currently being analysed.

[Post-traumatic proximal radioulnar synostosis. Surgical technique and review of the literature]. / Posttraumatische proximale radioulnare Synostose. Operationstechnik und Literaturübersicht.

Synostosis of the radioulnar joint can appear after severe fractures of the elbow, which leads to distinctive limitation in forearm rotation. We describe a surgical technique according to Morrey in a case of a young girl with resection osteotomy of the proximal radius without excision of the synostosis. Different therapeutic options for post-traumatic proximal radioulnar synostosis are discussed on the basis of the current literature.

[Removal of a bent intramedullary tibia nail. Case report and review of literature]. / Verbogener intramedullärer Tibiamarknagel nach erneutem Trauma. Fallbeschreibung und Literaturübersicht.

Breakage or deformity of intramedullary nails of the lower extremities is the result of subsequent high energy trauma, falling or noncompliance of the patient in partial weight bearing. We describe the removal of a bent tibia nail in a young patient who sustained another high energy trauma on the same limb. Different surgical options are discussed on the basis of the current literature. Possible removal strategies could be: drilling half diameter of the nail and then straighten it backwards, cutting the nail with a burr or removing the nail without any manipulation of the nail itself. The most customized procedure depends on the available capabilities and the individual case because of the rare occurrence of bent nails. Soft tissue damage, degree of bending and re-osteosynthesis must be considered in individual treatment strategies.

Collaborative study for the establishment of Ph. Eur. Human albumin (molecular size) Biological Reference Preparation batches 1, 2 and 3.

To comply with European Pharmacopoeia (Ph. Eur.) monograph Human albumin solution (0255), albumin solutions have to be tested for molecular-size distribution by size-exclusion chromatography (SEC). However, differences in interpretation of the test results continue to be observed among albumin manufacturers in Europe. A collaborative study was run by the European Directorate for the Quality of Medicines & HealthCare (EDQM), under the aegis of the Biological Standardisation Programme (BSP), to support the revision of Ph. Eur. monograph 0255 and to establish a Biological Reference Preparation (BRP) for use in the molecular-size distribution test. In 2019, Ph. Eur. Expert Group 6B proposed to include an analytical improvement of the SEC procedure in the monograph, which was then submitted for public enquiry. This publication describes the evaluation of three candidate BRPs to serve as a tool for both the system suitability test (SST) and albumin monomer and dimer peak identification according to the proposed revised methodology. Three Official Medicines Control Laboratories (OMCLs) involved in the official batch release of human albumin solution took part in the study. Based on the study results, the candidate BRPs were found suitable for purpose and were adopted by the Ph. Eur. Commission as Ph. Eur. Human albumin (molecular size) BRP batches 1, 2 and 3 concomitantly with the revised monograph Human albumin solution (0255) in November 2020.

Establishment of the Ph. Eur. erythropoietin chemical reference substance batch 1.

The Erythropoietin (EPO) European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch 3 was calibrated in 2006 by in vivo bioassay and was used as a reference preparation for these assays as well as for the physicochemical methods in the Ph. Eur. monograph Erythropoietin concentrated solution (1316). In order to avoid the frequent replacement of this standard and thus reduce the use of animals, a new EPO Chemical Reference Substance (CRS) was established to be used solely for the physicochemical methods. Here we report the outcome of a collaborative study aimed at demonstrating the suitability of the candidate CRS (cCRS) as a reference for the physicochemical methods in the Ph. Eur. monograph. Results from the study demonstrated that for the physicochemical methods currently required in the monograph (capillary zone electrophoresis (CZE), polyacrylamide gel electrophoresis (PAGE)/immunoblotting and peptide mapping), the cCRS is essentially identical to the existing BRP. However, data also indicated that, for the physicochemical methods under consideration for inclusion in a revised monograph (test for oxidised forms and glycan mapping), the suitability of the cCRS as a reference needs to be confirmed with additional work. Further to completion of the study, the Ph. Eur. Commission adopted the cCRS as "Erythropoietin for physicochemical tests CRS batch 1" to be used for CZE, PAGE/immunoblotting and peptide mapping.

Establishment of hepatitis A vaccine (inactivated, non-adsorbed) BRP batches 2 and 3.

The current hepatitis A vaccine (HAV), inactivated, non-adsorbed, European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) is used for the in vitro potency assay of HAV as prescribed by the Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. This reference preparation was calibrated in 2008 through an international collaborative study and was assigned a potency of 12 IU/mL. During use of this BRP it appeared to be inapplicable in certain cases due to a low nominal antigen content. Consequently, the European Directorate for the Quality of Medicines and HealthCare (EDQM) established replacement batches for this BRP, calibrated against the 1(st) WHO International Standard (IS) for HAV (inactivated), using the standard in vitro ELISA (enzyme-linked immunosorbent assay) method validated previously. The results of the study showed that the candidate BRPs were suitable for the intended purpose, and following completion of the study, they were adopted in November 2014 by the Ph. Eur. Commission as HAV (inactivated, non-adsorbed) BRP batches 2 and 3, with an assigned potency of 1350 IU/mL, for in vitro antigen content determination by ELISA. As the amount of material in each vial largely exceeds the amount required for the performance of a single assay, the BRPs are to be aliquoted by users as single-use aliquots and refrozen below -50 °C prior to their use as reference preparations.

Characterisation of steroid receptor expression in the human prostate carcinoma cell line 22RV1 and quantification of androgen effects on mRNA regulation of prostate-specific genes.

In this study, the effect of natural androgens on the expression of androgen-regulated genes in the human prostate carcinoma cell line 22RV1 was characterised. To clarify the usefulness of the cells for in vitro studies concerning activation of androgen responsive genes by various steroidal compounds steroid receptor expression patterns had to be characterised intensively. Expression of androgen receptor (AR), estrogen receptor alpha (ERalpha) and beta (ERbeta), progestin receptor (PR) and glucocorticoid receptor alpha and beta was investigated by the means of RT-PCR, immunocytochemistry, ligand binding or Western blot. 22RV1 cells were proved to express androgen receptor and less glucocorticoid receptor beta on mRNA level. The confirmed mutation of the androgen receptor at codon H874 slightly apart from the steroid binding pocket seemed not to cause alteration of natural steroid hormone binding. mRNA expression of all progestin and estrogen receptor isoforms as well as glucocorticoid receptor alpha could not be detected. To study functional relevance of above-mentioned findings nine androgen-regulated genes were chosen to characterise the cell line and to determine androgenic effects using highly sensitive real-time RT-PCR. Addition of the three natural steroids dihydrotestosterone (DHT), testosterone, and 19-nortestosterone significantly influenced mRNA expression profiles. All compounds under study showed clear time-dependent and androgen-specific effects on transcriptional level. The results demonstrate that the cultivated human prostate carcinoma epithelial cells have a hormonal sensitivity correlated with the presence of specific receptors and can, therefore, serve as a selective model to study hormone action.