CD73/5'-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells.

Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, ß-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/chondrogenic differentiation of MSCs and may provide a - thus far underestimated - therapeutic target to guide bone regeneration.

Defining the Gothic Arch Angle (GAA) as a radiographic diagnostic tool for instability in hip dysplasia.

In recent years, there has been a controversial discussion about whether borderline dysplastic hips should be treated with an arthroscopic procedure or rather with an acetabular reorientation. New research suggests that a classification into stable and unstable hips may be helpful. The aim of the study was to validate (1) the intra- and interobserver reliability of a newly defined radiographic parameter named the Gothic, (2) the association between the GAA and previously existing measurements used to define severity of acetabular dysplasia, and (3) the correlation between radiographic measurements of acetabular dysplasia with MRI findings previously suggestive of hip instability. We defined and validated the GAA in 10 standardized radiographs of asymptomatic hips by two observers and calculated intra- and interobserver coefficients at two individual dates. Subsequently, a consecutive series of 100 patients with dysplastic hips (LCEA < 25°, Toennis grade ≤ 1) were evaluated for signs of instability on anteroposterior (a.p.) pelvic radiographs and direct MR arthrography and were divided in two groups: stable and unstable. In these patients the LCEA, the AI, the FEAR index and the GAA were radiographically evaluated. Correlation analyses and a logistic regression analysis was performed to identify the predictive value of instability for each radiographic parameter. Cutoff probabilities analysis was performed using standard receiver operating characteristic (ROC) curves to rate the predictive efficiency value of the GAA. The GAA showed excellent inter- and intraobserver reliability. A correlation was found between GAA and FEAR index. A logistic regression analysis showed that LCEA, FEAR index and GAA are distinct predictors of instability in hip dysplasia. The GAA showed the largest area under the curve (AUC 0.96), indicating it to be the best predictor of instability with an optimal cutoff value of 90° (sensitivity, 0.95; specificity, 0.93). The GAA is a new available indicator for instability and is thus suggested to be used as a future radiographic parameter for the stability of dysplastic hips. Further studies are needed to understand how this parameter might additionally predict clinical outcome in the treatment of hip dysplasia.Level of evidence: Level III, diagnostic study.

Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study.

OBJECTIVES: The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). METHODS: The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. RESULTS: The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. CONCLUSION: The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species.Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12-19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2.

Alteraciones neurológicas durante el embarazo / Neurological alterations during pregnancy

Las diferentes patologías que se desarrollan durante el embarazo comprenden una variedad de situaciones que, sean simples o complejas en cuanto a la resolución, siempre generan al equipo de salud gran incertidumbre en el momento de abordarlas. Entre ellas, las alteraciones neurológicas, debido al espectro de enfermedades que pueden generarlas y a su impacto en la salud materno-fetal, representan un constante desafío. Esta revisión desarrolla los trastornos neurológicos más frecuentes durante el embarazo, su enfoque diagnóstico y terapéutico.(AU)

The different pathologies that develop during pregnancy include a variety of situations, whether simple or complex in their resolution that always generate great uncertainty to the health team at the time of the management. Among them, neurological disorders, due to the spectrum of diseases that can originate them and their impact on maternal and fetal health, represent a constant challenge. This review discusses the most common neurological disorders in pregnancy, their diagnosis and therapeutic approach.(AU)