Pulmonary choristoma in a new-born calf with multiple cranial and nervous malformations

ABSTRACT: Multiple congenital malformations can occur concomitantly in several species since the anomaly in one organ may lead directly to the malformation of another. Additionally, the etiology is not always clarified. Choristoma refers to an ectopic tissue that is histologically normal in an abnormal location. A case of pulmonary and nodal choristoma associated with cranioschisis, hydrocephalus, and syringomyelia in a new-born calf is reported here. Clinically, the calf had a mass in the frontal region of the head associated with local bone deformation. At necropsy, there was cranioschisis in the junction of the frontal bones and a 14 × 10 × 7 cm mass, grossly consistent with well-differentiated pulmonary tissue covered by skin, covering the opening between the frontal bones, and extending into the cranial cavity, leading to local cerebral compression. With the pulmonary choristoma, there was a well-differentiated lymphoid tissue. Additionally, in the central nervous system, there was severe hydrocephalus involving lateral ventricles and multiple areas of syringomyelia in the spinal cord.

Sustained Delivery of Lactoferrin Using Poloxamer Gels for Local Bone Regeneration in a Rat Calvarial Defect Model

Lactoferrin (LF) is a multifunctional milk glycoprotein that promotes bone regeneration. Local delivery of LF at the bone defect site is a promising approach for enhancement of bone regeneration, but efficient systems for sustained local delivery are still largely missing. The aim of this study was to investigate the potential of the poloxamers for sustained delivery of LF to enhance local bone regeneration. The developed LF/poloxamer formulations were liquid at room temperature (20 °C) transforming to a sustained releasing gel depot at body temperature (37 °C). In vitro release studies demonstrated an initial burst release (~50%), followed by slower release of LF for up to 72 h. Poloxamer, with and without LF, increased osteoblast viability at 72 h (p < 0.05) compared to control, and the immune response from THP-1 cells was mild when compared to the suture material. In rat calvarial defects, the LF/poloxamer group had lower bone volume than the controls (p = 0.0435). No difference was observed in tissue mineral density and lower bone defect coverage scores (p = 0.0267) at 12 weeks after surgery. In conclusion, LF/poloxamer formulations support cell viability and do not induce an unfavourable immune response; however, LF delivery via the current formulation of LF200/poloxamer gel did not demonstrate enhanced bone regeneration and was not compatible with the rat calvarial defect model.

Cortical bone thickness of the distal radius predicts the local bone mineral density

Aims The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). Methods A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability. Results The CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92). Conclusion The cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening. Cite this article: Bone Joint Res 2021;10(12):820–829.

The effect of cement augmentation on pedicle screw fixation under various load cases

Aims Anchorage of pedicle screw rod instrumentation in the elderly spine with poor bone quality remains challenging. Our study aims to evaluate how the screw bone anchorage is affected by screw design, bone quality, loading conditions, and cementing techniques. Methods Micro-finite element (µFE) models were created from micro-CT (μCT) scans of vertebrae implanted with two types of pedicle screws (L: Ennovate and R: S4). Simulations were conducted for a 10 mm radius region of interest (ROI) around each screw and for a full vertebra (FV) where different cementing scenarios were simulated around the screw tips. Stiffness was calculated in pull-out and anterior bending loads. Results Experimental pull-out strengths were excellently correlated to the µFE pull-out stiffness of the ROI (R2 > 0.87) and FV (R2 > 0.84) models. No significant difference due to screw design was observed. Cement augmentation increased pull-out stiffness by up to 94% and 48% for L and R screws, respectively, but only increased bending stiffness by up to 6.9% and 1.5%, respectively. Cementing involving only one screw tip resulted in lower stiffness increases in all tested screw designs and loading cases. The stiffening effect of cement augmentation on pull-out and bending stiffness was strongly and negatively correlated to local bone density around the screw (correlation coefficient ( R) = -0.95). Conclusion This combined experimental, µCT and µFE study showed that regional analyses may be sufficient to predict fixation strength in pull-out and that full analyses could show that cement augmentation around pedicle screws increased fixation stiffness in both pull-out and bending, especially for low-density bone. Cite this article: Bone Joint Res 2021;10(12):797–806.

Evaluation of in vitro biocompatibility of scaffolds for the repair of bone defects

The use of bone scaffolds in traumatology and orthopedics is an extremely important issue. The growing number of cases of significant bone defects, in particular after revision arthroplasty, combat trauma and due to the introduction of new methods of reconstructive surgery of bones and joints, requires more detailed studies of the using different osteoplastic materials. Materials and methods. As scaffolds used 4 types of materials that are most often used in the clinic for the correction of bone defects - ceramic hydroxylapatite, beta-tricalcium phosphate, allogeneic bone matrix treated with gamma irradiation, allogeneic bone matrix scaffold. The effect of matrices on the viability of normal human fibroblasts (M19 cell line) in cell culture in vitro was studied. The viability of cells after their co-cultivation with scaffolds was determined by colorimetric method by staining with crystal violet. To obtain an osteoinductive effect used platelet-rich plasma (PRP), standardized by the method of Araki with some modifications. The proliferative activity of fibroblasts was assessed by the level of expression of the proliferation marker Ki-67 by immunocytochemical analysis. Results. It was found that the least pronounced antiproliferative effect is shown by allogeneic bone matrix treated with gamma irradiation. Data on the complex effect of co-cultivation of fibroblasts with scaffolds in the presence of PRP on cell viability and proliferative activity were obtained. It was found that PRP improves the survival of fibroblasts by 15-30 % and increases their proliferative activity by 35-75 %. Delipidization of scaffold from allogeneic bone matrix, heat-treated by local bone bank technology, increased its biocompatibility with human fibroblasts. Conclusions. According to the results of a comparative analysis of the impact of different scaffolds on the viability of normal human fibroblasts, it was found that scaffolds from allogeneic bone matrix have the least pronounced antiproliferative effect. Platelet-rich plasma has been shown to improve fibroblast survival and increase their proliferative activity. Treatment with 70 % ethyl alcohol scaffold from allogeneic bone matrix, heat-treated by local bone bank technology, increased its biocompatibility with human fibroblasts.

Osteoblast-specific inactivation of p53 results in locally increased bone formation

Inactivation of the tumor suppressor p53 (encoded by the Trp53 gene) is relevant for development and growth of different cancers, including osteosarcoma, a primary bone tumor mostly affecting children and young adolescents. We have previously shown that deficiency of the ribosomal S6 kinase 2 (Rsk2) limits osteosarcoma growth in a transgenic mouse model overexpressing the proto-oncogene c-Fos. Our initial aim for the present study was to address the question, if Rsk2 deficiency would also influence osteosarcoma growth in another mouse model. For that purpose, we took advantage of Trp53fl/fl mice, which were crossed with Runx2Cre transgenic mice in order to inactivate p53 specifically in osteoblast lineage cells. However, since we unexpectedly identified Runx2Cre-mediated recombination also in the thymus, the majority of 6-month-old Trp53fl/fl;Runx2-Cre (thereafter termed Trp53Cre) animals displayed thymic lymphomas, similar to what has been described for Trp53-deficient mice. Since we did not detect osteosarcoma formation at that age, we could not follow our initial aim, but we studied the skeletal phenotype of Trp53Cre mice, with or without additional Rsk2 deficiency. Here we unexpectedly observed that Trp53Cre mice display a unique accumulation of trabecular bone in the midshaft region of the femur and the humerus, consistent with its previously established role as a negative regulator of osteoblastogenesis. Since this local bone mass increase in Trp53Cre mice was significantly reduced by Rsk2 deficiency, we isolated bone marrow cells from the different groups of mice and analyzed their behavior ex vivo. Here we observed a remarkable increase of colony formation, osteogenic differentiation and proliferation in Trp53Cre cultures, which was unaffected by Rsk2 deficiency. Our data thereby confirm a critical and tumorigenesis-independent function of p53 as a key regulator of mesenchymal cell differentiation.

Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1β, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.

Breast Cancer Recurrence Survival Among Iranian Patients; A 17-Year Retrospective Cohort Study

Background: Nowadays breast cancer (BC) is the most common cancer in women. More than 1.5 million cases are detected yearly. Survival of patients is dependent on several factors. Metastasis and cancer recurrence of different types and in different locations have various outcome. Methods: This is a retrospective cohort study to describe survival of patients after diagnosis of breast cancer based on receptor subtypes and sites of metastasis among Iranian population. A total number of 2051 females with breast cancer were evaluated and among these, 138 patients with recurrent BC were investigated. Results: The 1-year survival of local, bone, visceral and brain metastasis were 64.99%, 63%, 32.83%, and 21.57%, respectively. Based on sites of metastasis, bone and local metastasis showed the best survival while brain and visceral metastasis had the worst survival and prognosis. Conclusion: Our study showed that Her2 enriched positive BCs had the worst survival and triple negative receptor BC showed the best survival. This may be due to the discovery of Herceptin drugs for Her 2 enriched receptor breast cancers which ameliorates their prognosis and survival. Also, drugs related to luminal A and B which are used to improve their survival and hormonal therapy could be associated with their better prognosis in comparison to triple negative receptor subtype. Since our patients have not consumed Herceptin drugs over the last 17 years, the difference between our findings and those of other studies could be related to the release of this category of drugs.

Outcome of Breast Cancer Patients with COVID-19 Infection: A Report from a Tertiary Cancer Center in India

Background: Nowadays breast cancer (BC) is the most common cancer in women. More than 1.5 million cases are detected yearly. Survival of patients is dependent on several factors. Metastasis and cancer recurrence of different types and in different locations have various outcome. Methods: This is a retrospective cohort study to describe survival of patients after diagnosis of breast cancer based on receptor subtypes and sites of metastasis among Iranian population. A total number of 2051 females with breast cancer were evaluated and among these, 138 patients with recurrent BC were investigated. Results: The 1-year survival of local, bone, visceral and brain metastasis were 64.99%, 63%, 32.83%, and 21.57%, respectively. Based on sites of metastasis, bone and local metastasis showed the best survival while brain and visceral metastasis had the worst survival and prognosis. Conclusion: Our study showed that Her2 enriched positive BCs had the worst survival, this may be due to Trastuzumab uncovered insurance till 10 years ago in our country. Also, drugs related to luminal A and B which are used to improve their survival and hormonal therapy could be associated with their better prognosis in comparison to triple negative receptor subtype. But this study showed that triple negative BC had better survival.