Intramedullary nailing of femoral shaft fractures: an analysis of rotational malunions using 3D EOS.

PURPOSE: Rotational malalignment and leg length discrepancy after intramedullary nailing of femoral shaft are frequent. This study has three objectives: evaluate the rate of femoral rotational malalignment and leg length discrepancy using EOS imaging after antegrade intramedullary nailing of femoral shaft fracture, find a relevant clinical examination to detect malrotation and identified risk factors. METHODS: We performed a retrospective single-centre study between January 2014 and January 2022. Fifty-eight patients were clinically and radiographically assessed at a minimum of three months. RESULTS: The femoral rotation of the operated side was significantly greater by a mean of 15.4° in internal rotation compared to the healthy side. There was no statically significant difference for the femoral length (p = 0.08). CONCLUSION: When using EOS stereography following antegrade intramedullary nailing of post-traumatic diaphyseal femur fractures, a statistically significant difference of more than 15.4° in internal rotation was found for femoral rotation on the operated side compared to the healthy side.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [B. Poirot] Last name [Seynaeve]. Also, kindly confirm the details in the metadata are correct.The last name of the first author was corrected : Given name = B. and last name = Poirot Seynaeve The details in matadata are correct LEVEL OF EVIDENCE: III.

Novel Sternal Reconstruction With Custom Three-Dimensional-Printed Titanium PoreStar Prosthesis.

Resection of sternal tumors can leave large defects, which exposes major mediastinal structures, and can affect respiratory mechanics. If feasible, resection is potentially a complex reconstructive challenge to restore normal and functional anatomy using conventional techniques. We report the first Australian use of a three-dimensional-printed titanium and PoreStar prosthesis in a 39-year-old woman for reconstruction after major surgical resection of the sternum for metastatic breast cancer. The patient successfully underwent excision of the sternum and costal cartilages as well as implantation of the prosthesis. We conclude that three-dimensional-printed prostheses are technically feasible to deliver excellent cosmetic result.

P2 receptor stimulation induces amyloid precursor protein production and secretion in rat cortical astrocytes.

Amyloid precursor protein (APP) is ubiquitously expressed in a variety of tissues but is predominantly expressed in the brain. The expression of APP has been well studied in neurons but little is known about its presence in astrocytes. The study presented here shows that purinergic signaling is involved in the production and secretion of APP in primary cultures of rat cortical astrocytes. Extracellular ATP caused an increase in APP production and release in a time- and concentration-dependent manner and was inhibited by antagonists of P2 receptors. Further agonist and antagonist studies revealed involvement of P2Y2 and P2Y4 receptors in nucleotide-stimulated production and release of APP. In addition, signaling studies with various protein kinase inhibitors demonstrated that blockade of mitogen-activated protein kinases, but not Akt, inhibited nucleotide-stimulated APP expression and release. These results indicate that APP production and secretion can be regulated by activation of P2Y2/4 receptors coupled to protein kinase signaling pathways and suggest that astrocytes can be a potential source of APP.

Opposing effects of P2X(7) and P2Y purine/pyrimidine-preferring receptors on proliferation of astrocytes induced by fibroblast growth factor-2: implications for CNS development, injury, and repair.

Extracellular nucleotides play important trophic roles in development and central nervous system (CNS) injury, but the functions of distinct purinergic receptors and related signaling pathways have not been fully elucidated. In the present study we identified opposing effects of P2X and P2Y receptors on the ability of FGF2 to induce proliferation in primary cultures of rat cortical astrocytes. Low concentrations of ATP enhanced DNA synthesis induced by FGF2, whereas high concentrations inhibited FGF2-induced proliferation. Comparison of concentration-response experiments with ATP and 2',3'-O-(4-benzoyl)-benzoyl-ATP (BzATP) indicated that the inhibitory effect was mediated by P2X(7) receptors. Interestingly, activation of P2X(7) receptors led to a state of reversible growth arrest rather than cell death. Selectivity studies showed that proliferation evoked by epidermal growth factor and platelet-derived growth factor was also inhibited by P2X(7) receptors, but P2X(1) or P2X(3) receptors did not inhibit proliferation induced by FGF2. A marker of mitosis, phosphohistone-3, was reduced by BzATP and increased by UTP, suggesting that the enhancing effect of ATP on FGF2-induced proliferation was mediated by P2 purine/pyrimidine receptors. Phosphorylation of the growth arrest-related protein kinases p38/MAPK and SAPK/JNK was strongly increased by BzATP but only weakly affected by UTP. We conclude that P2Y purine/pyrimidine receptors enhance proliferation induced by FGF2 in astrocytes, whereas stimulation of P2X(7) receptors inhibits proliferation by shifting cells to a state of reversible growth arrest that may be mediated by protein kinase signaling. These trophic actions of P2X(7) and P2Y purine/pyrimidine receptors may contribute to the regulation of CNS development, adult neurogenesis, and the response of astrocytes to injury.

Purinergic receptor signaling regulates N-cadherin expression in primary astrocyte cultures.

Extracellular ATP exerts both short-term and long-term effects in the CNS by stimulating cell-surface purinergic receptors. Here we have examined the effect of purinergic receptor activation on N-cadherin expression, a calcium-dependent cell adhesion molecule involved in many processes, including glia-glia and axon-glia interactions. When primary cultures of rat cortical astrocytes were treated with ATP, N-cadherin protein expression increased in a time- and concentration-dependent manner. In addition, ATP treatment caused an increase in N-cadherin immunoreactivity in both the cytoplasm and on the cell surface membrane. Interestingly, experiments with cycloheximide revealed that relocalization of N-cadherin to the cell surface membrane were independent of protein synthesis. The ATP-induced increase in N-cadherin protein expression was blocked by reactive blue 2 and 8-(p-sulfophenyl)-theophylline, suggesting involvement of both P2 and P1 purinergic receptors, respectively. In addition, N-cadherin expression was partially blocked when signaling from purinergic receptors to extracellular signal regulated protein kinase or Akt was inhibited by 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene or wortmannin, respectively. By using an in vitro model of traumatic CNS injury, we found that N-cadherin expression was increased when astrocytes were subjected to rapid and reversible mechanical strain. The findings presented here demonstrate a role for extracellular ATP, purinergic receptors and protein kinase signaling in regulating N-cadherin expression and suggest a role for this mechanism in cell-cell interactions.

Purinergic signaling induces thrombospondin-1 expression in astrocytes.

Thrombospondin (TSP)-1, a multidomain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. However, little is known about the mechanisms regulating its expression and release. In this article, we report that purinergic signaling participates in the production and secretion of TSP-1. Treatment of primary cultures of rat cortical astrocytes with extracellular ATP caused an increase in TSP-1 expression in a time- and concentration-dependent manner and was inhibited by antagonists of P2 and P1 purinergic receptors. Agonist studies revealed that UTP, but not 2',3'-O-(4-benzoyl)benzoyl-ATP, 2-methylthio-ADP, adenosine, or 5'-N-ethyl-carboxamidoadenosine, caused a significant increase in TSP-1 expression. In addition, release of TSP-1 was stimulated by ATP and UTP but not by 2-methylthio-ADP or adenosine. Additional studies indicated that P2Y(4) receptors stimulate both TSP-1 expression and release. P2Y receptors are coupled to protein kinase cascades, and signaling studies demonstrated that blockade of mitogen-activated protein kinases or Akt inhibited ATP- and UTP-induced TSP-1 expression. Using an in vitro model of CNS trauma that stimulates release of ATP, we found that TSP-1 expression increased after mechanical strain and was completely blocked by a P2 receptor antagonist and by inhibition of p38/mitogen-activated protein kinase and Akt, thereby indicating a major role for P2 receptor/protein kinase signaling in TSP-1 expression induced by trauma. We conclude that TSP-1 expression can be regulated by activation of P2Y receptors, particularly P2Y(4), coupled to protein kinase signaling pathways and suggest that purinergic signaling may be an important factor in TSP-1-mediated cell-matrix and cell-cell interactions such as those occurring during development and repair.

P2 receptor signalling, proliferation of astrocytes, and expression of molecules involved in cell-cell interactions.

Growing evidence indicates that trophic actions of extracellular nucleotides are involved in CNS development, injury and repair. For example, upon CNS injury, ATP is released and contributes to the formation of reactive astrocytes, cells that produce molecules that can impede or promote axonal regeneration. Proliferation is one of the features of reactive astrogliosis, particularly in traumatic injury. Fibroblast growth factor (FGF)2 is also increased after injury and can stimulate astrocyte proliferation. Extracellular ATP enhances FGF2-induced proliferation in a process mediated by P2Y receptors and increased cyclin expression. However, when P2X receptors are activated, FGF2-induced proliferation is inhibited. P2 receptors are coupled to extracellular signal regulated protein kinase (ERK), and differences in the extent and duration of ERK activation by P2Y and P2X receptors may mediate the opposing effects of these receptors on FGF2-induced mitogenesis. Trauma also activates P2 receptor/ERK signalling, and stimulation of this and other protein kinase pathways by extracellular ATP increases expression of cell adhesion and extracellular matrix molecules involved in migration, glial contact formation, neuronal guidance and synapse formation. These findings support the hypothesis that purinergic signalling via protein kinase cascades plays a key role in astrocyte proliferation, glia-glia connections, and neuron-glia interactions in both normal and pathological conditions.

The Bali bombing: civilian aeromedical evacuation.

After the Bali bombing on 12 October 2002, many injured Australians required evacuation to Darwin, and then to burns units around Australia. Many patients were evacuated from Denpasar by Qantas, with assistance from staff of civilian medical retrieval services. The transport of patients from Darwin to specialist burns units involved a coordinated response of civilian and military services. Some issues in responding to such disasters were identified, and a national coordinating network could improve future responses.

Photoreceptor transplants increase host cone survival in the retinal degeneration (rd) mouse.

Retinal transplants offer a potentially interesting approach to treating human retinal degenerations, but so far little quantitative data are available on possible beneficial effects. We isolated photoreceptor layers from normal-sighted mice and grafted them into the subretinal space of retinal degeneration (rd) mice lacking rod photoreceptors. At 2 weeks after surgery, the numbers of residual host cone photoreceptors outside the graft zone were quantified following specific labelling. Examination of operated retinas revealed highly significantly greater numbers of surviving cones (mean of 38% more at 2 weeks) within the central field compared to sham-operated paired control retinas (p < 0.01). These are the first quantified data indicating a trophic effect of transplanted photoreceptors upon host cone cells. As cone cells are responsible for high acuity and colour vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to understanding underlying interactions between retinal photoreceptors.

[Retinal grafts: biological problems and clinical stakes]. / Greffes de rétine: problèmes biologiques et enjeux cliniques.

Retinal transplantation, formerly perceived as unrealistic, has become over the past decade a major clinical and biological undertaking in several laboratories and eye clinics. We describe the insights gained through the pioneering experimental works of Del Cerro et al, Turner et al, Gouras et al, Aramant et al, Lund et al e.g. the survival of transplants, the lack of immune response to photoreceptors, their integration and expression of neuronal markers, but also the dysplastic arrangement into rosettes and the lack of a definitive proof for functionality. Our laboratory has undertaken to establish the trophic and synaptic functions of sheets of photoreceptors transplanted, as described by Silverman et al, in the subretinal space of mutant rd mice carrying a retinal degeneration similar to human retinitis pigmentosa. Clinical applications to this condition as well as in cases of end-stage age related macular degeneration are discussed.