| 1. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Denk, Stephanie, et al.
(author)
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Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects
- 2017
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 198:12, s. 4846-4854
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Journal article (peer-reviewed)abstract
- During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pH(i)), we propose a direct mechanistic link between complement activation and neutrophil pHi. In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi. These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.
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| 3. |
- Ehrnthaller, Christian, et al.
(author)
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Complement C3 and C5 deficiency affects fracture healing.
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Journal article (peer-reviewed)abstract
- There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3(-/-) and C5(-/-) as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3(-/-): -25%, p=0.02; C5(-/-): -20% p=0.052) and newly formed bone (C3(-/-): -38%, p=0.01; C5(-/-): -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3(-/-) mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.
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| 4. |
- Leis-Peters, Annette, et al.
(author)
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A Common Spatial Scene? : Young People and Faith-Based Organisations at the Margins
- 2021
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In: Stuck in the Margins? Young people and faith-based organisations in South African and Nordic localities<em>. </em>. - Göttingen : Vandenhoeck & Ruprecht. - 9783525568552 - 9783666568558 ; , s. 247-265
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Book chapter (peer-reviewed)abstract
- This chapter shifts the focus to one of the overarching questions of the book on therole of faith-based organisations (FBOs) in dealing with the plight of young peopleat the margins in the selected South African and Nordic localities. The case studiesshow that FBOs have an important supportive function for many young peopleliving on the margins of society, even though they may play only a limited rolein fighting youth marginalisation in their respective local communities. Only fewFBO activities were directed pointedly at changing the situation of marginalisedyoung people. This does not mean that the FBOs did not help young people inneed; yet how they did this differed considerably between the Nordic and SouthAfrican contexts – and between metropolitan and rural or more remote areas. FBOsfunctioned as a spiritual and social resource, or sometimes even as the last safetynet, hence meeting the most acute existential needs of young people. At the sametime, however, they were not engaged in more systematic attempts to empowermarginalised young people. These similarities, differences and tensions evinced inthe results from the six case studies demanded deeper analysis and interpretation.
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| 5. |
- Sörensen, Jan Henrik, et al.
(author)
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Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo
- 2015
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In: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 6, s. 20-35
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Journal article (peer-reviewed)abstract
- The early fixation of bone screws after surgical implantation still remains a challenge in the fieldof traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developedto demonstrate that both implant fixation and safe removal are feasible in the same design. Accordinglythe aim of this study was to compare the in-vivo performance of thin biomimetic HA coatedtitanium screws to uncoated counterparts used as control after bilateral implantation in the femoralcondyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, byhistology, micro-CT and biomechanically at both two and six weeks post-implantation. The HAcoated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrateda significant increase in removal torque values as well as a strong trend towards higherpull-out forces. In addition histology confirmed a higher degree of osseointegration and directbone to implant contact. At six weeks no difference in pull-out force and removal torque could bedetected. SEM images confirmed the absence of any residual HA coating indicating a fast coatingdegradation in-vivo. The low level of removal torque after full osseointegration at 6 weeks supportsthe feasibility of safe and easy removal of the implant. The HA coating under study appearsto offer a unique characteristic of enhanced fixation with a minimal increase in removal torqueafter full osseointegration. This may be of value in clinical applications where it is necessary toassure both screw fixation and later removal.
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