Inadequate timing of prophylactic antibiotics in orthopedic surgery. We can do better

Background and purpose There are rising concerns about the frequency of infection after arthroplasty surgery. Prophylactic antibiotics are an important part of the preventive measures. As their effect is related to the timing of administration, it is important to follow how the routines with preoperative prophylactic antibiotics are working

Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute:<i>In vitro</i> and clinical release studies

OBJECTIVES: Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. MATERIALS AND METHODS: We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

Calcium Sulphate/Hydroxyapatite Carrier for Bone Formation in the Femoral Neck of Osteoporotic Rats

Final publication is available from Mary Ann Liebert, Inc., publishers https://www.liebertpub.com/doi/pdf/10.1089/ten.tea.2018.0075The authors would like to thank the Swedish Research Council (VR, grant no. 2015-06717), VINNOVA, the Swedish Agency for Innovation Systems (grant no. 2017-00269), and Department of Biotechnology, Government of India (BT/IN/ Sweden/08/AK/2017-18), for providing for the funding to conduct this stud

Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo

Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury. Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall

Osteoarthritis medical labelling and health-related quality of life in the general population

BACKGROUND: Osteoarthritis is the most common chronic joint disease. In the absence of an effective medical treatment and due to the chronic nature of this condition, an osteoarthritis medical diagnosis may finally result in decreased health-related quality of life. Therefore, the aim of this study was to measure the impact of the osteoarthritis medical labelling on physical and mental health-related quality of life. METHODS: Subjects (n = 1132, 58.7% women) were approached as participants of an urban population-based cohort (EPIPorto). Self-reported information on previous diagnosis of knee, hip or hand osteoarthritis was obtained and rheumatologists established knee, hip or hand osteoarthritis clinical diagnosis in symptomatic individuals. Physical and mental dimensions of health-related quality of life were evaluated using the self-administered Medical Outcomes Study: 36-Item Short Form Survey. Crude and adjusted linear regression coefficients (beta) and the corresponding 95% confidence intervals (95% CI) were computed to estimate the associations between being labelled as an osteoarthritis case and health-related quality of life. RESULTS: Regardless of disease medical labelling, individuals with osteoarthritis scored significantly lower physical health-related quality of life when compared to those without joint disease (knee(unexposed): beta = −5.3, 95% CI: −7.6, −3.1; knee(exposed): beta = −6.0, 95% CI: −8.4, −3.7; hip(unexposed): beta = −6.0, 95% CI: −9.8, −2.3; hip(exposed): beta = −11.0, 95% CI: −15.6, −6.4; hand(unexposed): beta = −4.3, 95% CI: −6.5, −2.0; hand(exposed): beta = −4.3, 95% CI: −6.6, −2.1). The same was not observed regarding mental health-related quality of life. Among subjects with clinically confirmed osteoarthritis, the medical labelling of this joint disease was not significantly associated to health-related quality of life. CONCLUSIONS: The labelling of knee, hip and hand osteoarthritis diagnosis may not add specific benefit to osteoarthritis patients in terms of its capability to improve health-related quality of life

Sustainable Food Systems At Urban Public Universities: A Survey Of U‐21 Universities

Urban communities are challenged by the conventional food system in diverse ways. To mitigate these challenges, a growing sustainable food system (SFS) movement mobilizes existing resources—including public institutions—to resolve disparities in access to healthy food, increase economic opportunities, conserve natural resources, and build a stronger, more local food system. Many public universities located in inner cities have adopted missions committing themselves to the improvement of their cities and regions. They also perform anchoring roles to revitalize their immediate neighborhoods, and, in a contemporary extension of their civic purposes, embrace sustainability as an institutional goal. Urban public universities therefore can play many SFS leadership roles, including through links to innovative scholarship, campus dining halls, other food retail such as farmers markets, and civic engagement activities such as community gardens. Through a study of 21 urban public universities, this paper investigates the presence and characteristics of SFS leadership, underlying rationales, and factors that support and oppose leadership.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112274/1/juaf12149.pd