3D analysis of Osteosyntheses material using semi-automated CT segmentation: a case series of a 4 corner fusion plate

Backround: Scaphoidectomy and midcarpal fusion can be performed using traditional fixation methods like K-wires, staples, screws or different dorsal (non) locking arthrodesis systems. The aim of this study is to test the Aptus four corner locking plate and to compare the clinical findings to the data revealed by CT scans and semi-automated segmentation. Methods: This is a retrospective review of eleven patients suffering from scapholunate advanced collapse (SLAC) or scaphoid non-union advanced collapse (SNAC) wrist, who received a four corner fusion between August 2011 and July 2014. The clinical evaluation consisted of measuring the range of motion (ROM), strength and pain on a visual analogue scale (VAS). Additionally, the Disabilities of the Arm, Shoulder and Hand (QuickDASH) and the Mayo Wrist Score were assessed. A computerized tomography (CT) of the wrist was obtained six weeks postoperatively. After semi-automated segmentation of the CT scans, the models were post processed and surveyed. Results: During the six-month follow-up mean range of motion (ROM) of the operated wrist was 60 degrees, consisting of 30 degrees extension and 30 degrees flexion. While pain levels decreased significantly, 54% of grip strength and 89% of pinch strength were preserved compared to the contralateral healthy wrist. Union could be detected in all CT scans of the wrist. While X-ray pictures obtained postoperatively revealed no pathology, two user related technical complications were found through the 3D analysis, which correlated to the clinical outcome. Conclusion: Due to semi-automated segmentation and 3D analysis it has been proved that the plate design can keep up to the manufacturers' promises. Over all, this case series confirmed that the plate can compete with the coexisting techniques concerning clinical outcome, union and complication rate

Interleukin-1 beta single-nucleotide polymorphism\u27s C allele is associated with elevated risk of gastric cancer in helicobacter pylori-infected Peruvians

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru

The C allele of the IL-1B-511 SNP is associated with higher risk for Gastric Cancer and its premalignant lesion - a prospective case-control study in Peru

von Sebastian Gehmer

Lipolytic effects of nano particle sized polyenylphosphatidylcholine on adipose tissue: First promising in vitro and in vivo results

BACKGROUND: Lipolytic injectables for body contouring procedures have been reported for necrotic effects on adipose tissue causing side effects as swelling, pain and hematoma. Deoxycholic acid is widely used as a solvent in lipolytic injectables and is associated with necrosis when applied to cells. A new lipolytic preparation (NWL-10) containing only polyenylphosphatidylcholine in nano particle size, glycerrhizinate and maltose has been reported for its lipolytic action on adipose tissue. However, no data exist whether the NWL-10 mixture is responsible for apoptosis or necrosis in adipose tissue which can be associated with severer side effects as reported for deoxycholic acid preparation. METHODS: 3T3-L1 mouse cells and human adipose tissue derived stem cells were exposed to the NWL-10 mixture and to each ingredient of the mix in order to investigate cytotoxic, lipolytic, necrotic or apoptotic effects. Furthermore, a Balb/C mouse animal model was used to investigate inflammatory responses to NWL-10 by bioluminescence monitoring and histological examination. RESULTS: A high extent of lipolysis was detected for the NWL-10 mixture when applied to both cell types with no cytotoxic effect. Interestingly, low concentration of NWL-10 resulted in necrosis whereas high concentration of NWL-10 showed a certain amount of apoptosis. Application of single ingredients of NWL-10 or various combinations of two component mixtures did not result in any apoptosis or necrosis. In addition, no inflammatory effects of NWL-10 were observed in the mouse model. CONCLUSIONS: The NWL-10 mixture provided promising results regarding lipolysis on adipose tissue with limited apoptosis and necrosis when compared to currently available injectables. These first promising results require further fundamental and more detailed research on essentials for drug approval. NWL-10 has the potential to become a second generation product for future lipolytic injectables

Transcription Profile in Sporadic Multiple Symmetric Lipomatosis Reveals Differential Expression at the Level of Adipose Tissue–Derived Stem Cells

Background: The cause of the rare fat distribution disorder multiple symmetric lipomatosis is unknown. Independent reports suggest a higher proliferative activity, hormone resistance, and involvement of mitochondrial function in the disease. Methods: The authors performed morphologic comparison of affected and unaffected tissues in five unrelated patients and generated adipose-derived stem cell cultures from the tissue samples and characterized them as a possible cellular model of multiple symmetric lipomatosis evolution. The authors investigated proliferative activity and the expression of genes relevant to disease processes. Results: There was no difference in the morphologic appearance and the surface marker profile. Stem cells from lipomatous tissue showed significantly higher proliferative activity. Polymerase chain reaction arrays showed marked changes in genes associated with proliferation, hormonal regulation, and mitochondria. The authors show that multiple symmetric lipomatosis tissue is morphologically and histologically different from regular subcutaneous fat. Conclusions: This study indicates an involvement of mesenchymal stem cells in the pathogenesis of multiple symmetric lipomatosis and that the evolution of multiple symmetric lipomatosis tissue is a process driven by an inherent defect of the respective cell clone(s). Further molecular genetics and functional analysis will be required to unravel the pathogenetic mechanism underlying the derailment in fat cell metabolism and proliferation. Here, the authors show for the first time that adipose-derived stem cells exhibit many characteristics previously described for native multiple symmetric lipomatosis fat tissue and propose that they are therefore an excellent tool for further functional investigations in multiple symmetric lipomatosis and other disorders of the fat tissue. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V

PDGF regulated migration of mesenchymal stem cells towards malignancy acts via the PI3K signaling pathway

INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation. MATERIALS AND METHODS: Breast cancer cell lines were purchased and ASC's were isolated from murine subcutaneous adipose tissue. The transmigration of ASC' s towards the PDGF-isoforms was assessed by using recombinant human PDGF-AA, PDGF-BB and PDGF-CC in a trans-well culture dish system. Transmigrated ASC's were quantified in 5 randomly selected fields per condition using fluorescence microscopy after calcein-staining. PDGF-BB depended transmigration of ASC' s was verified by downregulation and overexpression of PDGF-BB in breast cancer cell line using lentiviral vectors. In addition, a PI3-kinase inhibitor (LY294002) and a MAP-kinase inhibitor (PD98059) were used to identify the pathway involved in the PDGF-BB mediated migration of ASC's towards tumor. RESULTS: ASC' s transmigration significantly increased towards PDGF AA at 50 ng and only showed further increase by 500 ng which was similar to cell behavior when exposed to PDGF CC. In comparison, PDGF-BB significantly increased ASC's transmigration already at a low level of 5 ng with further significant increase for 20 ng and 40 ng. Cell transmigration was blocked with PDGFR-alpha antibodies but only for PDGF-AA and PDGF-CC whereas PDGFR-beta blockage showed a significant effect on transmigration for PDGF-BB and PDGF-CC but not for PDGF-AA. Neutralizing antibodies in combination with PDGF receptor blockage confirmed findings. In addition, only PI3-kinase inhibitor but not the MEK-1 selective inhibitor caused a significant decrease of transmigration for ASCs towards breast cancer cells. DISCUSSION: The transmigration of ASC's is most significantly enhanced by PDGF-BB via the PI3-kinase pathway. This data support that PI3-kinase is an important key player for MSC migration towards malignancy which need further research to prevent tumor progression in early disease stage

Interaction between extracellular cancer matrix and stromal breast cells

INTRODUCTION: Stromal-epithelial interactions are fundamental for normal organ development and there is a multitude of evidence that the different components of the microenvironment are also necessary for the maintenance and promotion of the "tumor organ". Deregulated tumor associated extracellular matrix (tECM) is a hallmark of cancer, causing an alteration in the amount and composition of the different components (i.e. proteins, proteoglycans, glycoproteins and polysaccharids) of the ECM. As epithelial-stromal interactions are reciprocal, it is possible that tECM itself is able to initiate tumor development. We therefore established a mouse model to examine the influence of tECM of murine breast cancer on developing breast tissue in mice. MATERIALS AND METHODS: Breast cancer was established in 5 BALB/c mice by subcutaneous injection of 1 x 10(6) 4T1 cells in 100 mu l PBS into the left mammary fat pad. The mammary fat pad including the primary tumor was excised after two weeks, decellularised and labelled as tumor extracellular matrix (tECM). Tumor ECM of 4T1 tumors was implanted into the 4th inguinal mammary fat pad of BALB/c mice (n = 5) aged 5 days. After 12 weeks the fourth mammary fat pad including the primary tumor was excised. Tissue was used for paraffin embedding and mouse breast cancer PCR array. Murine breast cancer tissue (BCT) and normal murine breast tissue (BT) served as control. RESULTS: Gene array analysis of 84 breast cancer-specific transcripts revealed that the mammary gland cells which were exposed to tumor ECM (tECM-BT) showed a similarly high overexpression for 22 genes as apparent for breast cancer tissue (BCT). The corresponding scatter plot showed a high agreement in the expression of the examined genes between the mammary gland cells which were exposed to tumor ECM and the breast cancer tissue. DISCUSSION: Our results clearly demonstrate that the tECM is able to shift the gene expression pattern of murine mammary epithelial cells towards that of carcinoma, indicating a role in breast cancer initiation. These data underlines that the acellular component of the tumor (ECM) can lead to a transformation of mammary gland tissue cells. These data show for the first time that the interaction of normal breast tissue cells with tumor ECM leads to an exchange of information and a consecutive overexpression of tumor-specific genes

Effects on the Distal Radioulnar Joint of Ablation of Triangular Fibrocartilage Complex Tears With Radiofrequency Energy

Purpose This cadaver study investigated the temperature profile in the wrist joint and distal radioulnar joint (DRUJ) during radiofrequency energy (RFE) application for triangular fibrocartilage complex resection. Methods An arthroscopic partial resection of the triangular fibrocartilage complex using monopolar and bipolar RFE was simulated in 14 cadaver limbs. The temperature was recorded simultaneously in the DRUJ and at 6 other anatomic locations of the wrist during RFE application. Results The mean temperature in the DRUJ was 43.3 +/- 8.2 degrees C for the bipolar system in the ablation mode (60 W) and 30.4 +/- 3.4 degrees C for the monopolar system in the cut mode (20 W) after 30 seconds. The highest measured temperature in the DRUJ was 54.3 degrees C for the bipolar system and 68.1 degrees C for the monopolar system. Conclusions The application of RFE for debridement or resection of the triangular fibrocartilage complex in a clinical setting can induce peak temperatures that might cause damage to the cartilage of the DRUJ. Bipolar systems produce higher mean temperatures than monopolar devices. Clinical relevance RFE application increases the mean temperature in the DRUJ after 30 seconds to a level that may jeopardize cartilage tissue. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.

Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases