Jumper's fracture of the sacrum: a novel and reproducible way for successful reduction and fixation

PURPOSE Surgical treatment of jumper's fractures is a highly demanding situation for the surgeon due to its rareness and frequent association with severe concomitant injuries. There is no current consensus regarding a standard treatment approach, thus reducing quality of care. Our objectives were to describe, apply and assess a novel surgical technic. METHODS The presented research is an observational retrospective study of patients who underwent the described novel surgical intervention in a level 1 trauma center. We conducted analyses of the patient cohort using patient-related outcome measures at least 1 year after surgery, as well as investigating pain, quality of life and the clinical effectiveness of the procedure. RESULTS A total of 24 patients (17 male and 7 female) with an average age 47 ± 16.3~years were included. ISS scores ranged from 9 to 66 with a mean ISS of 40 ± 15. Clinical scores exist of 15 out of 24 patients (62.5%). The mean VAS score was 53.7 ± 12.9. The mean EQ-5D index was 0.68 ± 0.22. Significant negative correlation existed between the ISS value and the EQ-5D index (r = - 0.704; p < 0.005) and EQ-5D VAS (r = - 0.809; p < 0.001). Anatomical reduction was achieved in all patients (n = 24). Radiological follow-up was performed in 58%. CONCLUSION We present one of the largest studies with operatively treated jumper's fractures of the sacrum. The technique is capable of reproducibly restoring the physiological anatomy of the patient and allows pain-adapted mobilization

Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries

Background: Surgical treatment of unstable syndesmotic injuries is not trivial, and there are no generally accepted treatment guidelines. The most common controversies regarding surgical treatment are related to screw fixation versus dynamic fixation, the use of reduction clamps, open versus closed reduction, and the role of the posterior malleolus and of the anterior inferior tibiofibular ligament (AITFL). Our aim was to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by the literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm. Methods: PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries were searched independently by two reviewers using specific terms and limits. Surgical principles supported by the literature were fused into an evidence-based surgical treatment algorithm. Results: A total of 171 articles were included for further considerations. Among them, 47 articles concerned syndesmotic screw fixation and 41 flexible dynamic fixations of the syndesmosis. Twenty-five studies compared screw fixation with dynamic fixations, and seven out of these comparisons were randomized controlled trials. Nineteen articles addressed the posterior malleolus, 14 the role of the AITFL, and eight the use of reduction clamps. Anatomic reduction is crucial to prevent posttraumatic osteoarthritis. Therefore, flexible dynamic stabilization techniques should be preferred whenever possible. An unstable AITFL should be repaired and augmented, as it represents an important stabilizer of external rotation of the distal fibula. Conclusions: The current literature provides sufficient arguments for the development of an evidence-based surgical treatment algorithm for unstable syndesmotic injuries

The molecular fingerprint of lung inflammation after blunt chest trauma

Abstract Background After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown. Methods Therefore, inflammation in lung tissue following blunt chest trauma was characterized in a well-defined bilateral lung injury model. Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined. Results The results suggest an activation of a highly complex transcriptional program in response to chest trauma. Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator). However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper). Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca2+ channel). Conclusions Taken together, the provided global perspective of the inflammatory response following blunt chest trauma could provide a molecular framework for future research in trauma pathophysiology.http://deepblue.lib.umich.edu/bitstream/2027.42/113091/1/40001_2015_Article_164.pd

Правове регулювання безоплатної приватизації земель запасу

Досліджуються правові підстави безоплатної приватизації земель запасу. Автор виокремлює два її різновиди – гарантовану і негарантовану. Розкриваються особли­вості багатоетапної процедури реалізації права на безоплатну приватизацію земель запасу в Україні.Исследуются правовые основания бесплатной приватизации земель запаса. Автор разделяет два ее разновидности – гарантированную и негарантированную. Раскрыва­ются особенности многоэтапной процедуры реализации права на бесплатную прива­тизацию земель в Украине.Legal rules about free of payment land privatization are investigated. The author pro­poses dividing free of payment land privatization into two varieties: guaranteed and non­guaranteed ones. Legal peculiarities of multistoried procedure of free of payment land priva­tization in Ukraine are disclosed

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5–10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/FP7-HEALTH-2009); REBORNE Project (GA: 241876

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions

Background and study aim: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture. Patients and methods: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni). Results: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation. Conclusion: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers

Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

publishedVersio

Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis

Funding Information: This work was supported by the European Regional Development Fund (ERDF) grant Nr. 1.1.1.2/VIAA/1/16/144 “Structural and functional studies of Lyme disease agent Borrelia burgdorferi outer surface proteins to reveal the mechanisms of pathogenesis with the intention to create a new vaccine”. Diffraction data have been collected on BL14.1 at the BESSY II electron storage ring operated by the Helmholtz-Zentrum, Berlin. We would particularly like to acknowledge the help and support of Manfred S. Weiss and Christian Feiler during the experiment. Publisher Copyright: © 2018, The Author(s).Borrelia (B.) bavariensis, B. burgdorferi, B. afzelii, B. garinii, B. spielmanii, and B. mayonii are the causative agents in Lyme disease. Lyme disease spirochetes reside in infected Ixodes ticks and are transferred to mammalian hosts during tick feeding. Once transmitted, spirochetes must overcome the first line of defense of the innate immune system either by binding complement regulators or by terminating the formation of the membrane attack complex (MAC). In B. bavariensis, the proteins BGA66 and BGA71 inhibit complement activation by interacting with the late complement components C7, C8, and C9, as well as with the formed MAC. In this study, we have determined the crystal structure of the potent MAC inhibitor BGA71 at 2.9 Ǻ resolution. The structure revealed a cysteine cross-linked homodimer. Based on the crystal structure of BGA71 and the structure-based sequence alignment with CspA from B. burgdorferi, we have proposed a potential binding site for C7 and C9, both of which are constituents of the formed MAC. Our results shed light on the molecular mechanism of immune evasion developed by the human pathogenic Borrelia species to overcome innate immunity. These results will aid in the understanding of Lyme disease pathogenesis and pave the way for the development of new strategies to prevent Lyme disease.publishersversionPeer reviewe

On the functional overlap between complement and anti-microbial peptides

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C₃ involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C₃ is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia)