Radial head and neck fractures in children and adolescents

BackgroundRadial head and neck fractures are a rare entity in pediatric patients. Due to specific characteristics of the blood supply and remodeling potential, the correct diagnosis and initiation of appropriate therapy are crucial for the outcome. Therefore, the aim of this retrospective observational study was to present the outcome of a series of pediatric patients with radial head and neck fractures.MethodsIn total, 67 pediatric and adolescent patients with a fracture of the proximal radius admitted to a Level I Trauma Center (Germany) between 2005 and 2017 were included in this retrospective observational study. Patients were stratified in accordance with the classification of Judet modified by Metaizeau and with the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF).ResultsAO-PCCF fracture type of proximal radius was age-dependent. Epiphyseal axis angle and displacement angle correlated significantly. Fractures treated with a K-wire or embrochage centromedullaire elastique stable (ECMES) presented higher displacement angles. The duration of callus formation was dependent on both the reduction technique and fracture displacement. The range of motion after complete fracture consolidation was dependent on the Metaizeau type and reduction technique but independent of the duration of immobilization and physical therapy.Conclusion and clinical relevanceBoth the epiphyseal axis and displacement angle are suitable for measuring the initial fracture displacement in radiographs. Consolidation is dependent on the initial displacement and reduction technique. The mini-open approach leads to a worse reduction result, later callus formation, and a more restricted range of motion in terms of pronation. Furthermore, the range of motion at follow-up is independent of the duration of immobilization and physiotherapy

Cellular activation status in femoral shaft fracture hematoma following different reaming techniques - A large animal model

The local inflammatory impact of different reaming protocols in intramedullary nailing has been sparsely investigated. We examined the effect of different reaming protocols on fracture hematoma (FH) immunological characteristics in pigs. To do so, a standardized midshaft femur fracture was induced in adult male pigs. Fractures were treated with conventional reamed femoral nailing (group RFN, n = 6); unreamed femoral nailing (group UFN, n = 6); reaming with a Reamer Irrigator Aspirator device (group RIA, n = 12). Animals were observed for 6 h and FH was collected. FH-cell apoptosis and neutrophil receptor expression (Mac-1/CD11b and FcγRIII/CD16) were studied by flow cytometry and local temperature changes were analyzed. The study demonstrates that apoptosis-rates of FH-immune cells were significantly lower in group RIA (3.50 ± 0.53%) when compared with non-RIA groups: (group UFN 12.50 ± 5.22%, p = 0.028 UFN vs. RIA), (group RFN 13.30 ± 3.18%, p < 0.001, RFN vs. RIA). Further, RIA-FH showed lower neutrophil CD11b/CD16 expression when compared with RFN (mean difference of 43.0% median fluorescence intensity (MFI), p = 0.02; and mean difference of 35.3% MFI, p = 0.04, respectively). Finally, RIA induced a transient local hypothermia and hypothermia negatively correlated with both FH-immune cell apoptosis and neutrophil activation. In conclusion, immunologic changes observed in FH appear to be modified by certain reaming techniques. Irrigation during reaming was associated with transient local hypothermia, decreased apoptosis, and reduced neutrophil activation. Further study is warranted to examine whether the rinsing effect of RIA, specific tissue removal by reaming, or thermal effects predominantly determine local inflammatory changes during reaming

Complementâ induced activation of the cardiac NLRP3 inflammasome in sepsis

Cardiac dysfunction develops during sepsis in humans and rodents. In the model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we investigated the role of the NLRP3 inflammasome in the heart. Mouse heart homogenates from shamâ procedure mice contained high mRNA levels of NLRP3 and ILâ 1β. Usingthe inflamm a some protocol, exposure of cardiomyocytes (CMs) to LPS followed by ATP or nigericin caused release of mature ILâ 1β. Immuno staining of left ventricular frozen sections before and 8 h after CLP revealed the presence of NLRP3 and ILâ 1β proteins inCMs. CLP caused substantial increases in mRNAs for ILâ 1β and NLRP3 in CMs which are reduced in the absence of either C5aR1 or C5aR2. After CLP, NLRP32/2 mice showed reduced plasma levels of ILâ 1βand ILâ 6. In vitro exposure of wildâ type CMs to recombinant C5a (rC5a) cause delevations in both cytosolic and nuclear/mitochondrial reactive oxygen species (ROS), which were C5aâ receptor dependent. Use of a selective NOX2 inhibitor prevented increased cytosolic and nuclear/mitochondrial ROS levels and release of ILâ 1β. Finally, NLRP32/2 mice had reduced defects in echo/Doppler parameters in heart afterCLP. These studies establish that the NLRP3 inflammasome contributes to the cardiomyopathy of polymicrobial sepsis.â Kalbitz, M., Fattahi, F., Grailer, J. J., Jajou, L., Malan, E. A., Zetoune, F. S., Huberâ Lang, M., Russell, M. W., Ward, P. A. Complementâ induced activation of the cardiac NLRP3 inflammasome in sepsis. FASEB J. 30, 3997â 4006 (2016). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154362/1/fsb2fasebj30120728r.pd

Complementâ induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction

Polymicrobial sepsis in mice causes myocardial dysfunction after generation of the complement anaphylatoxin, complement component 5a (C5a). C5a interacts with its receptors on cardiomyocytes (CMs), resulting in redox imbalance and cardiac dysfunction that can be functionally measured and quantitated using Doppler echocardiography. In this report we have evaluated activation of MAPKs and Akt in CMs exposed to C5a in vitro and after cecal ligation and puncture (CLP) in vivo. In both cases, C5a in vitro caused activation (phosphorylation) of MAPKs and Akt in CMs, which required availability of both C5a receptors. Using immunofluorescence technology, activation of MAPKs and Akt occurred in left ventricular (LV) CMs, requiring both C5a receptors, C5aR1 and â 2. Use of a waterâ soluble p38 inhibitor curtailed activation in vivo of MAPKs and Akt in LV CMs as well as the appearance of cytokines and histones in plasma from CLP mice. When mouse macrophages were exposed in vitro to LPS, activation of MAPKs and Akt also occurred. The copresence of the p38 inhibitor blocked these activation responses. Finally, the presence of the p38 inhibitor in CLP mice reduced the development of cardiac dysfunction. These data suggest that polymicrobial sepsis causes cardiac dysfunction that appears to be linked to activation of MAPKs and Akt in heart.â Fattahi, F., Kalbitz, M., Malan, E. A., Abe, E., Jajou, L., Huberâ Lang, M. S., Bosmann, M., Russell, M. W., Zetoune, F. S., Ward, P. A. Complementâ induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction. FASEB J. 31, 4129â 4139 (2017). www.fasebj.orgâ Fattahi, Fatemeh, Kalbitz, Miriam, Malan, Elizabeth A., Abe, Elizabeth, Jajou, Lawrence, Huberâ Lang, Markus S., Bosmann, Markus, Russell, Mark W., Zetoune, Firas S., Ward, Peter A., Complementâ induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction. FASEB J. 31, 4129â 4139 (2017)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154261/1/fsb2fj201700140r.pd

Cardiac Glucose and Fatty Acid Transport After Experimental Mono- and Polytrauma

OBJECTIVE The aim of this study was to define the influence of trauma on cardiac glucose and fatty acid transport. The effects were investigated in vivo in a porcine mono- and polytrauma model and in vitro in human cardiomyocytes, which were treated simultaneously with different inflammatory substances, mimicking post-traumatic inflammatory conditions. METHODS AND RESULTS In the porcine fracture- and polytrauma model, blood glucose concentrations were measured by blood gas analysis during an observation period of 72 h. The expression of cardiac glucose and fatty acid transporters in the left ventricle was determined by RT-qPCR and immunofluorescence. Cardiac and hepatic glycogen storage was examined. Furthermore, human cardiomyocytes were exposed to a defined trauma-cocktail and the expression levels of glucose- and fatty acid transporters were determined. Early after polytrauma, hyperglycaemia was observed. After 48 h and 72 h, pigs with fracture- and polytrauma developed hypoglycaemia. The propofol demand significantly increased post trauma. The hepatic glycogen concentration was reduced 72 h after trauma. Cardiac glucose and fatty acid transporters changed in both trauma models in vivo as well as in vitro in human cardiomyocytes in presence of proinflammatory mediators. CONCLUSIONS Monotrauma as well as polytrauma changed the cardiac energy transport by altering the expression of glucose and fatty acid transporters. In vitro data suggest that human cardiomyocytes shift to a state alike myocardial hibernation preferring glucose as primary energy source in order to maintain cardiac function

Successful Resuscitation in a Model of Asphyxia and Hemorrhage to Test Different Volume Resuscitation Strategies. A Study in Newborn Piglets After Transition

Background: Evidence for recommendations on the use of volume expansion during cardiopulmonary resuscitation in newborn infants is limited.Objectives: To develop a newborn piglet model with asphyxia, hemorrhage, and cardiac arrest to test different volume resuscitation on return of spontaneous circulation (ROSC). We hypothesized that immediate red cell transfusion reduces time to ROSC as compared to the use of an isotonic crystalloid fluid.Methods: Forty-four anaesthetized and intubated newborn piglets [age 32 h (12–44 h), weight 1,220 g (1,060–1,495g), Median (IQR)] were exposed to hypoxia and blood loss until asystole occurred. At this point they were randomized into two groups: (1) Crystalloid group: receiving isotonic sodium chloride (n = 22). (2) Early transfusion group: receiving blood transfusion (n = 22). In all other ways the piglets were resuscitated according to ILCOR 2015 guidelines [including respiratory support, chest compressions (CC) and epinephrine use]. One hour after ROSC piglets from the crystalloid group were randomized in two sub-groups: late blood transfusion and infusion of isotonic sodium chloride to investigate the effects of a late transfusion on hemodynamic parameters.Results: All animals achieved ROSC. Comparing the crystalloid to early blood transfusion group blood loss was 30.7 ml/kg (22.3–39.6 ml/kg) vs. 34.6 ml/kg (25.2–44.7 ml/kg), Median (IQR). Eleven subjects did not receive volume expansion as ROSC occurred rapidly. Thirty-three animals received volume expansion (16 vs. 17 in the crystalloid vs. early transfusion group). 14.1% vs. 10.5% of previously extracted blood volume in the crystalloid vs. early transfusion group was infused before ROSC. There was no significant difference in time to ROSC between groups [crystalloid group: 164 s (129–198 s), early transfusion group: 163 s (162–199 s), Median (IQR)] with no difference in epinephrine use.Conclusions: Early blood transfusion compared to crystalloid did not reduce time to ROSC, although our model included only a moderate degree of hemorrhage and ROSC occurred early in 11 subjects before any volume resuscitation occurred

Role of extracellular histones in the cardiomyopathy of sepsis

The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca2+]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nachtâ , LRRâ , and PYDâ domainsâ containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca2+]i, as wellas defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction.â Kalbitz, M., Grailer, J. J., Fattahi, F., Jajou, L., Herron, T. J., Campbell, K. F., Zetoune, F. S., Bosmann, M., Sarma, J. V., Huberâ Lang, M., Gebhard, F., Loaiza, R., Valdivia, H. H., Jalife, J., Russell, M. W., Ward, P. A. Role of extracellular histones in the cardiomyopathy of sepsis. FASEB J. 29, 2185â 2193 (2015). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154273/1/fsb2fj14268730.pd

Altered early immune response after fracture and traumatic brain injury

IntroductionClinical and preclinical data suggest accelerated bone fracture healing in subjects with an additional traumatic brain injury (TBI). Mechanistically, altered metabolism and neuro-endocrine regulations have been shown to influence bone formation after combined fracture and TBI, thereby increasing the bone content in the fracture callus. However, the early inflammatory response towards fracture and TBI has not been investigated in detail so far. This is of great importance, since the early inflammatory phase of fracture healing is known to be essential for the initiation of downstream regenerative processes for adequate fracture repair.MethodsTherefore, we analyzed systemic and local inflammatory mediators and immune cells in mice which were exposed to fracture only or fracture + TBI 6h and 24h after injury.ResultsWe found a dysregulated systemic immune response and significantly fewer neutrophils and mast cells locally in the fracture hematoma. Further, local CXCL10 expression was significantly decreased in the animals with combined trauma, which correlated significantly with the reduced mast cell numbers.DiscussionSince mast cells and mast cell-derived CXCL10 have been shown to increase osteoclastogenesis, the reduced mast cell numbers might contribute to higher bone content in the fracture callus of fracture + TBI mice due to decreased callus remodeling

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use