Wedge volume and osteotomy surface depend on surgical technique for distal femoral osteotomy

Purpose

Biplanar distal femoral osteotomy (DFO) is thought to promote rapid bone healing due to the increased cancellous bone surface compared to other DFO techniques. However, precise data on the bone surface area and wedge volume resulting from both open- and closed-wedge DFO techniques remain unknown. We hypothesized that biplanar rather than uniplanar DFO better reflects the ideal geometrical requirements for bone healing, representing a large cancellous bone surface combined with a small wedge volume.

Methods

Femoral saw bones were assigned to 4 different groups of varization distal femur osteotomies: group 1, lateral open-wedge uniplanar DFO; group 2, medial closed-wedge uniplanar DFO; group 3, lateral open-wedge biplanar DFO; and group 4, medial closed-wedge biplanar DFO. Bone surface areas of all osteotomy planes were quantified. Wedge volumes were determined using a prism-based algorithm, applying standardized wedge heights of 5, 10 and 15 mm.

Results

The biplanar osteotomy techniques (groups 3 and 4) created significantly larger femoral surface compared to the uniplanar groups (groups 1 and 2) (p = 0.036). Bone surfaces after the lateral biplanar open-wedge technique (group 3) were slightly larger than the medial biplanar closed-wedge technique (group 4) and biplane techniques significantly larger than the uniplanar techniques (groups 1 and 2). Wedge volumes were significantly higher in the lateral uniplanar open-wedge (group 1) and biplanar open-wedge (group 3) techniques compared to the closed-wedge techniques (groups 2 and 4) that have nearly absent wedge volumes.

Conclusion

Bone geometry following DFO suggests that the medial biplanar closed-wedge technique simultaneously creates smaller wedge volume and larger bone surface areas compared to the lateral biplanar open-wedge and the uniplanar DFO techniques. The horizontal cuts of the biplane DFO techniques are positioned behind the trochlear area in better healing metaphysial bone, which further enhances bone healing potential. Although this idealized geometric view on bony geometry excludes all biological factors that influence bone healing, the current data confirm the general rule for osteotomy techniques: reducing the amount of slow gap healing and wedge volumes and simultaneously increasing the area of faster contact healing by larger bone surface areas may be beneficial for osteotomy healing.     

Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Purpose

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

Methods

The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.

Results

The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.

Conclusions

Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.

Level of evidence

IV.     

Grading system for the selection of patients with congenital aural atresia for active middle ear implants

Introduction

Active middle ear implants (aMEI) are being increasingly used for hearing restoration in congenital aural atresia. The existing gradings used for CT findings do not meet the requirements for these implants. Some items are expendable, whereas other important imaging factors are missing. We aimed to create a new grading system that could describe the extent of the malformation and predict the viability and challenges of implanting an aMEI.

Methods

One hundred three malformed ears were evaluated using HRCT of the temporal bone. The qualitative items middle ear and mastoid pneumatization, oval window, stapes, round window, tegmen mastoideum displacement and facial nerve displacement were included. An anterior- and posterior round window corridor, oval window and stapes corridor were quantified and novelly included. They describe the size of the surgical field and the sight towards the windows.

Results

The ears were graded on a 16-point scale (16–13 easy, 12–9 moderate, 8–5 difficult, 4–0 high risk). The strength of agreement between the calculated score and the performed implantations was good. The comparison of the new 16-point scale with the Jahrsdoerfer score showed that both were able to conclusively detect the high-risk group; however, the new 16-point scale was able to further determine which malformed ears were favorable for aMEI, which the Jahrsdoerfer score could not do.

Conclusion

The Active Middle Ear Implant Score for aural atresia (aMEI score) allows more precise risk stratification and decision making regarding the implantation. The use of operative corridors seems to have significantly better prognostic accuracy than the Jahrsdoerfer score.     

Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival

Glioblastoma (GBM) is the most malignant brain tumor where patients'' survival is only 14.6 months, despite multimodal therapy with debulking surgery, concurrent chemotherapy and radiotherapy. There is an urgent, unmet need for novel, effective therapeutic strategies for this devastating disease. Although several immunotherapies are under development for the treatment of GBM patients, the use of natural killer (NK) cells is still marginal despite this being a promising approach to treat cancer. In regard of our knowledge on the role of NG2/CSPG4 in promoting GBM aggressiveness we investigated the potential of an innovative immunotherapeutic strategy combining mAb9.2.27 against NG2/CSPG4 and NK cells in preclinical animal models of GBM. Multiple immune escape mechanisms maintain the tumor microenvironment in an anti-inflammatory state to promote tumor growth, however, the distinct roles of resident microglia versus recruited macrophages is not elucidated. We hypothesized that exploiting the cytokine release capabilities of activated NK cells to reverse the anti-inflammatory axis combined with mAb9.2.27 targeting the NG2/CSPG4 may favor tumor destruction by editing pro-GBM immune responses. Combination treatment with NK+mAb9.2.27 diminished tumor growth that was associated with reduced tumor proliferation, increased cellular apoptosis and prolonged survival compared to vehicle and monotherapy controls. The therapeutic efficacy was mediated by recruitment of CCR2^low macrophages into the tumor microenvironment, increased ED1 and MHC class II expression on microglia that might render them competent for GBM antigen presentation, as well as elevated IFN-γ and TNF-α levels in the cerebrospinal fluid compared to controls. Depletion of systemic macrophages by liposome-encapsulated clodronate decreased the CCR2^low macrophages recruited to the brain and abolished the beneficial outcomes. Moreover, mAb9.2.27 reversed tumor-promoting effects of patient-derived tumor-associated macrophage/ microglia (TAM) ex vivo. Taken together, these findings indicate that NK+mAb9.2.27 treatment may be an amenable therapeutic strategy to treat NG2/CSPG4 expressing GBMs. We provide a novel conceptual approach of combination immunotherapy for glioblastoma. The results traverse beyond the elucidation of NG2/CSPG4 as a therapeutic target, but demonstrate a proof of concept that this antibody may hold potential for the treatment of GBM by activation of tumor infiltrated microglia/macrophages.     

Blockade of the PDGFR family together with SRC leads to diminished proliferation of colorectal cancer cells

Among the family of receptor tyrosine kinases (RTKs), platelet-derived growth factor receptor (PDGFR) has attracted increasing attention as a potential target of anti-tumor therapy in colorectal cancer (CRC). To study the function of PDGFRβ in CRC cell lines, SW480, DLD-1 and Caco-2 cells showing high PDGFRβ expression were used for receptor down-regulation by small interfering RNA (siRNA) and using the pharmacological inhibitor of PDGFRβ Ki11502. Blockade of PDGFRβ using both approaches led to moderate inhibition of proliferation and diminished activation of the downstream PI3K-signaling pathway in all three cell lines. Surprisingly, incubation with Ki11502 resulted in an arrest of SW480 cells in the G2 phase of the cell cycle, whereas the siRNA approach did not result in this effect. To address this difference, we analyzed the involvement of the PDGFRβ family member c-KIT in Ki11502 effectiveness, but siRNA and proliferation studies in SW480 and DLD-1 cells could not prove the involvement of c-KIT inactivation during Ki11502 treatment.Hence, an RTK activation antibody array on SW480 cells led us to the identification of the non-receptor tyrosine kinase SRC, which is inactivated after Ki11502 treatment but not after the siRNA approach. Further studies using the SRC-specific inhibitor PP2 showed that SRC inhibition upon treatment with the inhibitor Ki11502 is responsible for the observed effects of Ki11502 in SW480 and DLD-1 CRC cells. In summary, our results demonstrate that the inhibition of PDGFRβ alone using siRNA has only moderate cellular effects in CRC cell lines; however, the multi-target inhibition of PDGFRβ, c-KIT and SRC, e.g., using Ki11502, represents a promising therapeutic intervention for the treatment of CRC.     

Prosthodontic biomaterials and adverse reactions: a critical review of the clinical and research literature

Prosthodontic biomaterials include impression materials, luting cements, and restorative materials. They consist of metals and alloys ceramics, and polymer materials and are retained in patients for <60 min or for decades. Oral release of compounds from biomaterials occurs, and adverse reactions may follow dental treatment. Especially in allergically vulnerable patients contact allergy may occur. There are reports from many different countries on contact allergy from gold/palladium alloys, components from polymer-based materials, chromium/cobalt alloys, and nickel. Notifications on adverse reactions in Norway, Sweden, and England are handled by a registry in which patient reactions and occupational exposure are recorded. Data from The Adverse Reaction Unit in Bergen and Ume? have been a most valuable basis in extending knowledge in a field of current interest in dentistry. A review of the clinical and research literature relating to prosthodontic biomaterials and adverse reactions shows that reliable methods seem necessary to expose the frequency of adverse reactions in general dentistry, including prosthodontic treatment.     

Multiple neural signatures of social proof and deviance during the observation of other people's preferences

Detecting one's agreement with or deviation from other people, a key principle of social cognition, relies on neurocognitive mechanisms involved in reward processing, mismatch detection, and attentional orienting. Previous studies have focused on explicit depictions of the (in)congruency of individual and group judgments. Here, we report data from a novel experimental paradigm in which participants first rated a set of images and were later simply confronted with other individuals’ ostensible preferences. Participants strongly aligned their judgments in the direction of other people's deviation from their own initial rating, which was neither an effect of regression toward the mean nor of evaluative conditioning (Experiment 1). Most importantly, we provide neurophysiological evidence of the involvement of fundamental cognitive functions related to social comparison (Experiment 2), even though our paradigm did not overly boost this process. Mismatches, as compared to matches, of preferences were associated with an amplitude increase of a broadly distributed N400‐like deflection, suggesting that social deviance is represented in the human brain in a similar way as conflicts or breaches of expectation. Also, both early (P2) and late (LPC) signatures of attentional selection were significantly modulated by the social (mis)match of preferences. Our data thus strengthen and valuably extend previous findings on the neurocognitive principles of social proof.