Der Einfluss der Schrittlänge auf die plantare Druckverteilung bei Patienten mit diabetischem Fußsyndrom

Bei Patienten mit dem Diabetischen Fußsyndrom besteht die Gefahr von Ulzerationen,welche bei erhöhtem plantaren Fussdruck zunimmt.Der Einfluss der Schrittlänge auf den plantaren Druck ist bisher nur unzureichend bekannt und soll mit dieser Studie näher untersucht werden.Material/Methoden:An 19 diabetischen Patienten (ohne akute Fußläsionen) werden die Konsequenzen einer Schrittlängenverkürzung erforscht. Allen Patienten wird ein elastisches Trippelband angebracht, das die Schrittweite in definierter Weise begrenzt. Die Auswirkungen auf den Fußdruck werden mit dem kapazitivem Messsystem PEDAR (Novel, München) gemessen und in 6 Fußregionen analysiert. Ergebnisse: Es zeigt sich eine signifikante Abnahme der plantaren Druckverteilung bei verkürzter Schrittlänge. Besonders in der gefährdeten Region unter dem Ballen verringert sich sowohl der Maximaldruck als auch der mittlere Druck

Learning how to perform ultrasound-guided interventions with and without augmented reality visualization: a randomized study

OBJECTIVES Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using AR ultrasound (AR US) compared with standard US (sUS). METHODS Forty-four medical students (28 women, 16 men) who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality. The experimental setup aimed to simulate biopsies of superficial soft tissue lesions, such as for example breast masses in clinical practice, by use of a turkey breast containing olives. Time to puncture(s) and success (yes/no) of the biopsies was documented. All participants completed questionnaires about their coordinative skills and their experience during the training. RESULTS Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6-60] and 14.5 s [5-41], p = 0.16), nor were there any gender-related differences (p = 0.22 and p = 0.50). AR US was considered by 79.5% of the operators to be the more enjoyable means of learning and performing US-guided biopsies. Further, a more favorable learning curve was achieved using AR US. CONCLUSIONS Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS. KEY POINTS • Performance of standard and augmented reality US-guided biopsies was comparable • A more favorable learning curve was achieved using augmented reality US. • Augmented reality US was the preferred technique and was considered more enjoyable

Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis

OBJECTIVE: In the present study we evaluated the decrease of cartilage destruction by a novel orally active and specific MMP-13 inhibitor in three different animal models of rheumatoid arthritis (RA). MATERIALS AND METHODS: The SCID mouse co-implantation model of RA, collagen-induced arthritis (CIA) model in mice and the antigen induced arthritis model (AIA) in rabbits were used. RESULTS: In the SCID mouse co-implantation model this inhibitor resulted in reduced cartilage destruction by 75%. In the CIA model of RA, the MMP-13 inhibitor resulted in a significant and dose dependent decrease in clinical symptoms as well as of cartilage erosion by 38% (30 mg/kg), 28% (10 mg/kg) and 21% (3 mg/kg). No significant effects were observed in the AIA model. No toxic effects were observed in all three animal models. CONCLUSION: Although several MMPs in concert with other proteinases play a role in the process of cartilage destruction, there is a need for highly selective MMP inhibitors to reduce severe side effects that occur with non-specific inhibitors. Significant inhibition of MMP-13 reduced cartilage erosions in two out of three tested animal models of RA. These results strongly support the development of this class of drugs to reduce or halt joint destruction in patients with RA

TLR3 ligand poly(I:C) exerts distinct actions in synovial fibroblasts when delivered by extracellular vesicles

Extracellular vesicles (EV) can modulate the responses of cells to toll-like receptor (TLR) ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA) can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA) are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs) from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C), a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C)-stimulated U937 cells [Poly(I:C) EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C) EV contain or associate with Poly(I:C) and at least partially protect Poly(I:C) from RNAse III degradation. Poly(I:C) EV shuttle Poly(I:C) to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C). Poly(I:C) EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C). These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C) and may reflect the route of Poly(I:C) deliveryEV or the fine-tuning of Poly(I:C) actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the expansion of the invasive synovial stroma)

Treatment strategies for periprosthetic infections after primary elbow arthroplasty

BACKGROUND: The goal of this study was to investigate the outcome of different surgical procedures (debridement and retention vs 1- or 2-stage exchange) together with a well-defined antimicrobial regimen. MATERIALS AND METHODS: A total of 236 consecutive patients underwent 262 primary elbow arthroplasties between January 1994 and December 2007. We observed 20 episodes of periprosthetic infections in 19 patients and placed them into 3 groups according to the occurrence of infection after index surgery. A total of 9 early infections (24 months) were observed. The treatment among those 3 groups was compared, and the outcome was assessed with a mean follow-up of 60.2 months. RESULTS: In the group with early infections (n = 9), 8 cases were treated by irrigation and debridement and 1 case was treated by a 2-stage exchange without recurrence of infection. The mean Mayo Elbow Performance Score improved from 48.3 points (range, 30-75 points) to 91.7 points (range, 85-100 points). The delayed infection was treated by 1-stage exchange without recurrence of infection. For late infections (n = 10), 3 cases presented recurrence of infection after debridement and irrigation, and the mean Mayo Elbow Performance Score remained nearly unchanged, from 60 points (range, 45-80 points) to 65 points (range, 50-80 points). Eradication of infection could be achieved by staged revision and in 3 cases by debridement. CONCLUSION: Both debridement with retention and staged reimplantation are highly successful for appropriate indications. Staged revisions are successful even against biofilm-active microorganisms, but a prosthesis-free interval of at least 3 months is recommended

Learning how to perform ultrasound-guided interventions with and without augmented reality visualization: a randomized study

Objectives Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using AR ultrasound (AR US) compared with standard US (sUS). Methods Forty-four medical students (28 women, 16 men) who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality. The experimental setup aimed to simulate biopsies of superficial soft tissue lesions, such as for example breast masses in clinical practice, by use of a turkey breast containing olives. Time to puncture(s) and success (yes/no) of the biopsies was documented. All participants completed questionnaires about their coordinative skills and their experience during the training. Results Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6–60] and 14.5 s [5–41], p = 0.16), nor were there any gender-related differences (p = 0.22 and p = 0.50). AR US was considered by 79.5% of the operators to be the more enjoyable means of learning and performing US-guided biopsies. Further, a more favorable learning curve was achieved using AR US. Conclusions Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS.ISSN:0938-7994ISSN:1432-108

Evaluating the bromodomain protein BRD1 as a therapeutic target in rheumatoid arthritis

Targeting epigenetic reader proteins by small molecule inhibitors represents a new therapeutic concept in autoimmune diseases such as rheumatoid arthritis (RA). Although inhibitors targeting bromodomain protein 1 (BRD1) are in development, the function of BRD1 has hardly been studied. We investigated the therapeutic potential of BRD1 inhibition in joint-resident cells in RA, synovial fibroblasts (SF) and macrophages. The proliferation of SF was decreased upon BRD1 silencing, accompanied by the downregulation of genes involved in cell cycle regulation. Silencing of BRD1 in SF decreased the basal expression of MMP1 but increased TNF-α- and LPS-induced levels of MMP3, IL6 and IL8. In monocyte-derived macrophages (MDM), silencing of BRD1 decreased the LPS-induced expression of TNF-α, but did not significantly affect basal and the TNF-α- and LPS-induced expression of IL6 and IL8. Our data point to a cell type- and a stimulus-specific function of BRD1. Inhibiting BRD1 could have potential beneficial effects in RA via decreasing the proliferation of SF. Anti-inflammatory effects were limited and only observed in MDM